Supporting Online Material for:

Nuclear receptor ERRα and coactivator PGC-1β are

effectors of IFN-γ induced host defense

Junichiro Sonoda, Josée Laganière, Isaac Mehl, Grant Barish, Ling-Wa Chong, Xiangli Li, Immo E. Scheffler, Dennis C. Mock, Alain R. Bataille, François Robert, Chih-Hao Lee, Vincent Giguère and Ronald M. Evans

This PDF includes:

Materials and Methods for Online Supplemental Figures

References for Supporting Online Material

Legends for Online Supplemental Figures

Figures S1 to S17

Tables S1 to 6

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Online Supplemental Materials and Methods

Cell

STAT-1 deficient macrophages were obtained by differentiating bone marrow cells from STAT-1

KO mice (Meraz et al. 1996) (Taconic). Stable RAW cell lines were obtained by a standard method by infecting parental RAW264 cells with the pBABE-puro retroviral vector, followed by selection with puromycin. In the stable RAW-VP-ERRα cell line, VP-ERRα is constitutively expressed under the control of Moloney Murine Leukemia Virus long terminal repeats. For Q-PCR analysis of nuclear and mitochondrial DNA, total DNA digested with NotI was used as a template. Sequences of primers used are: Nuclear DNA: 5'-GTGGTTGAACCTGAGAAGCTGTAC-3' and 5'-

TCGATCAAAAAGGTCACAGAGAGT-3'; Mitochondria DNA: 5'-

TTTTAATTCGAGCAGAATTAGGTCAA-3' and

5'-AAAGCATGGGCAGTTACGATAAC-3'

Immunostaining of macrophages was carried out using affinity purified anti-ERRα antibody (NLS5402: Novus) and Cy3 labeled secondary antibody (Jackson Immuno Laboratory).

FACS analysis

Splenocytes were prepared at day 2 post Listeria infection (2X104 c.f.u) by mechanical processing.

Cells were filtered through 70µM strainer and red blood cells in spleen were removed by hypotonic lysis. The cell populations (1x106 cells) were identified with monoclonal antibodies directed against surface markers (BD PharMingen, eBiosciences, or Invitrogen) as previously described (King et al.

2004). Positively stained populations were determined by gating against isotype control antibodies.

Samples were analyzed using a flow cytometer (Digital LSRII; BD Biosciences) and FlowJo software. Dead cells and doublets were excluded from the analysis by side and forward scatter. For the analysis of surface marker expressions in BMDM, monoclonal antibodies, anti-Mac-1, -

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FcgRIII/II, - Gr-1 (BD Pharmingen) and anti-F4/80 (Serotec), were used, and analyses were conducted using FACS Scan (Becton Dickinson) and CellQuest software (Becton Dickinson).

References for Online Supplemental Methods

King, C., Ilic, A., Koelsch, K., and Sarvetnick, N. 2004. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell 117(2): 265-277. Meraz, M.A., White, J.M., Sheehan, K.C., Bach, E.A., Rodig, S.J., Dighe, A.S., Kaplan, D.H., Riley, J.K., Greenlund, A.C., Campbell, D., Carver-Moore, K., DuBois, R.N., Clark, R., Aguet, M., and Schreiber, R.D. 1996. Targeted disruption of the Stat1 in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84(3): 431- 442.

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Legends for Online Supplemental Figures

Figure S1. FACS analysis of surface marker expression in WT and ERRα KO macrophages. Solid line: Mac-1, FcgRIII/II, F4/80 are macrophage markers and Gr-1 is a granurocyte marker. Gray: isotype control. No significant difference was observed between WT and ERRα KO macrophages.

Figure S2. Cytokine-induced expression of activation markers in ERRα KO macrophages. Q-PCR mRNA expression normalized by U36B4 expression. BMD-macrophages are treated with indicated cytokines for 12 hrs before RNA was prepared. n=4. iNOS and arginase are markers for IFN-γ- or

IL-4-dependent activation respectively.

Figure S3. Subcellular localization of potential ERRα targets. GFP fused to a potential

ERRα target identified by oligo DNA microarray were transiently expressed in COS7 cells, stained with a mitochondria marker dye, Mitotracker and fixed. The images were obtained by confocal microscopy. Green: GFP, Red: Mitotracker. Note that 1110007M04, 5730472N09, D10Ertd214E colocalized with Mitotracker, whereas D530030D03, 9530058B02 and Ubadc1 did not.

Figure S4. ERRα-dependent induction of mitochondria by IFN-γ and IL-4. Q-PCR mRNA expression of ERRα target genes (A) and non-ERRα target genes (B). Relative expression normalized by U36B4 expression is shown. BMD-macrophages are treated with indicated cytokines for 12 hrs before RNA was prepared. n=4. No significant difference between WT and KO was observed for mtTFA, Ucp1, Ucp2, Ucp3, Mcad, Vlcad or PGC-1β.

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Figure S5. ERRα-dependent induction of mitochondria genes by IFN-γ. Q-PCR mRNA expression of ERRα target genes (A) and non-ERRα target genes (B) involved in oxidative metabolism or inflammation in WT and ERRα KO macrophages. Relative expression normalized by 36B4 expression is shown. BMD-macrophages are treated with IFN-γ for indicated time (hrs) before

RNA was prepared. n=4.

Figure S6. Binding of ERRα to target gene promoters. / complexes were precipitated from IFN-γ-treated or mock-treated macrophages using ERRα antibody, and subjected to Q-PCR. Note that ERRα binds to its target gene promoters even in the absence of IFN-γ treatment. Although we repeatedly observed a slight augmentation of ERRα recruitment in the presence of IFN-γ, the significance is not clear. When ERRα KO cells were used, no enrichment of the genes shown was observed (data not shown).

Figure S7. Nuclear accumulation of the ERRα protein in macrophages treated with IFN-γ or IL-4.

Expression of ERRα protein (green) in macrophages was examined using ERRα-specific antibody at 8 hrs after addition of indicated cytokines. Blue: DAPI for DNA staining.

Figure S8. Promoter binding of ERRα in IFN-γ-treated macrophages. Chromatin/protein complexes were precipitated from IFN-γ-treated macrophages using ERRα antibody, and hybridized to a mouse promoter DNA chip. The wheel represents all the 215 genes (with GO functions) that were identified. The genes identified in both the genome-wide expression of IFN-γ treated cells and promoter-binding experiments are listed around the wheel (red: mitochondrial genes; black: other location). Two genes had no function assigned to them (listed below the

5

categories). The genes that were also identified by the IFN-γ/IL-4 comparison (Table S1) are shown with bold letter. Asterisks indicate genes that were not identified by the promoter DNA chip, but were positive by the conventional chromatin immunoprecipitation (Table S3).

Figure S9. Q-PCR analysis of nuclear and mitochondrial DNA content in macrophages. Q-PCR analysis of nuclear and mitochondrial DNA content. Macrophages are cultured with or without IFN-

γ in the presence of M-CSF for 36 hrs before isolation of total DNA. Results are shown as a relative ratio of mitochondrial(mt) DNA/nuclear(nuc) DNA. n=3.

Figure S10. An increased ROS production by a constitutively active form of ERRα. (A) Transient transfection assay showing that VP16-ERRα fusion protein (VP-ERRα) induce transcription of a target reporter gene without IFN-γ treatment in murine macrophages cell line RAW264.

RAW cells were cotransfected with an expression vector for mouse ERRα, VP-ERRα or a control vector (none) together with CMX-gal and a luciferase reporter harboring three copies of ERRα from murine IDH3A gene. Transfected cells were incubated with media for 48 h before luciferase and β-galactosidase assays. The results represent the average of triplicate experiments.

(B) RT-PCR showing expression of mRNA encoding VP-ERRα fusion protein in stably transduced

RAW macrophage cell lines. STAT3: loading control. (C) Density plot of representative FACS analysis for ROS production using dichlorofluorescein. (gray: RAW-vec, open: RAW-VP-ERRα)

Figure S11. Infection of cultured macrophages with LM: the effects of inhibitors. In vitro LM infection of activated macrophages. Macrophages pretreated with IFN-γ together with iNOS inhibitor L-NMMA or NADPH oxidase inhibitor apocynin for 36 hours were infected with MOI=1

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LM, incubated for 15 min without antibiotics to allow infection, then for indicated time with gentamicin to kill extracellular LM. The number of intracellular viable LM was determined 5 hours post infection by plating serial dilutions of cell lysate onto agar plates. Significant difference between WT and ERRα KO; * p<0.03, ** p<0.003, *** p<0.04. n=3.

Figure S12. Serum cytokine levels in LM infected mice. Serum was prepared at day 2 post LM infection (2X104 c.f.u), and cytokine levels were quantitatively determined by using monoclonal antibody against indicated cytokines. * Significant difference between uninfected and infected samples of the same genotype (p<0.05), n=4 (-LM) and 8 (+LM). No significance (p<0.05) was observed between WT and KO.

Figure S13. Expression of gene encoding cytokine or other inflammation marker in spleens from

LM infected mice. Total RNA was prepared from spleen isolated at day 2 post LM infection

(2X104 c.f.u), and expression of mRNA encoding indicated cytokines were quantitatively determined by Q-PCR. No significance (p<0.05) was observed between WT and KO. n=4 (-LM) and 8 (+LM).

Figure S14. STAT1-dependent induction by IFN-γ. Q-PCR mRNA expression of

STAT-1 target genes (A) and ERRα target genes in WT and STAT-1 KO macrophages. Relative expression normalized by U36B4 expression is shown. BMD-macrophages are treated with indicated cytokines for 12 hrs before RNA was prepared. n=3.

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Figure S15. FACS analysis of surface marker expression in WT and PGC-1β KO macrophages.

Solid line: Mac-1, FcgRIII/II, F4/80 are macrophage markers and Gr-1 is a granurocyte marker.

Gray: isotype control. No significant difference was observed between WT and PGC-1β KO macrophages.

Figure S16. ERRα- and PGC-1β-dependent induction of mitochondria genes by IFN-γ and IL-4.

Q-PCR mRNA expression of ERRα target genes in WT, ERRα KO and PGC-1β KO macrophages.

Relative expression normalized by U36B4 expression is shown. BMD-macrophages are treated with indicated cytokines for 12 hrs before RNA was prepared. n=4. No significant difference between

WT and KO was observed for arginase expression.

Figure S17. (GO) pathways whose expression were significantly different between

WT and PGC-1β KO. The numbers of genes identified for each pathway are shown at right.

8 Sonoda_FigS1 Mac-1 FcγRIII/II F4/80 Gr-1

ERRα+/+

Green Fluorescence Green Fluorescence Green Fluorescence Green Fluorescence

ERRα-/-

Green Fluorescence Green Fluorescence Green Fluorescence Green Fluorescence

Sonoda_FigS2

3000 4 WT 3000 WT WT 3 2000 KO 2000 KO KO 2 1000 1 1000 0 0 0

30 2 800 WT 1.5 WT 600 WT 20 KO 1 KO 400 KO 10 0.5 200 0 0 0

Sonoda_FigS3

1110007M04 5730472N09 D10Ertd214E

D530030D03 9530058B02 Ubadc1 Sonoda_FigS4 A CytC Atp5b Atp5g 3 4 3 3 2 2 2 1 1 1 0 0 0

Cox8a Ndufs7 Sdhd 3 2 2 2

1 1 1

0 0 0

Timm13a Coq7 4 3 3 2 2 +/+ -/- 1 1 0 0

B

Ucp1 Ucp2 Ucp3 3 4 2 2 3 2 1 1 1 0 0 0

Mcad Vlcad Pgc-1β 3 16 1 2 12 WT 0.5 8 KO 1 4 0 0 0

+/+ -/- Sonoda_FigS5 A

5 10 5 4 Coq7 CytC Atp5b Atp5g3 8 4 4 3 3 6 3 2 2 4 2 1 1 2 1

0 0 0 0 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24

3 5 4 4 Sdha Cox8a Ndfs7 Sdhd 4 3 3 2 3 2 2 2 1 1 1 1

0 0 0 0 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24

6 3 3 30 Aco2 Idh3a Timm13a Ndg2 5 25 2 2 4 20 3 15 1 1 2 10 1 5

0 0 0 0 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 B 3 3 4 Gabpa Gabpb2 Nur77 3 2 2 2 1 1 1

0 0 0 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 +/+

30000 20 3 -/- iNOS PGC1β Mcad 25000 15 20000 2

15000 10 10000 1 5 5000 0 0 0 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 Sonoda_FigS6

20 mock 16 IFN-γ 12 8 Fold enrichment 4

0 Control ERRα Atp5g3 Aco2

Sonoda_FigS7

Mock IFN-γ IL-4

Sonoda_FigS8

Ap1g2 Got2 Timm10 metabolism Supv3l1 Glycolysis/carbohydrate metabolism Cell growth/adhesion/migration biogenesis Csf2rb2 DNA metabolism ERRα Heme metabolism Zpf142 Aco2* Cox7a2 Ndufs1 Inflammatory response Atp5b Cox8a Suclg1 Immune response 215 PROMOTERS Atp5c1 Cycs Ndufs3 /steroid metabolism Atp5d* Idh3a* Ndufs7 OXPHOS/TCA cycle Atp5g3 Ndufa5 Sdha Atp5k Ndufa9 Sdhb* Protein modification/metabolism Coq7 Ndufb4 Sdhd RNA processing/metabolism Cox5b Ndufb5 1110020P15Rik Signal transduction Transcriptional regulation Transport Comtd1 Hspa9a Hbold2 C530044N13Rik Sonoda_FigS9

WT KO 1.4 1.2 1 0.8 0.6 0.4 0.2 0 mock IFN-γ

Sonoda_FigS10

A B C 4 RAW-vec +RT -RT RAW-VP-ERRα 3

ERRα VP 2

1

VP-ERR 0 α 101 102 STAT3 fluorescence

Sonoda_FigS11

4E+04 WT ** KO 3E+04 * *** 2E+04

1E+04

mock L-NMMA apocynin Sonoda_FigS12

TNF-α IL-12 (p70) 800 1200 * * 700 * 1000 600 800 500 WT WT 400 600 KO KO 300 400 200 200 100 0 0 -LM +LM -LM +LM

IL-12 (p40) IL-18 1600 2000 1400 1200 1500 1000 WT WT 800 1000 KO KO 600 400 500 200 0 0 -LM +LM -LM +LM

IL-15 3500 3000 2500 2000 WT 1500 KO 1000 500 0 -LM +LM Sonoda_FigS13

IFN-γ TNF-α 2.5 2 2 1.5 1.5 WT WT 1 1 KO KO 0.5 0.5 0 0 -LM +LM -LM +LM

IL-1β IL-12 2 2 1.5 1.5 WT WT 1 1 KO KO 0.5 0.5 0 0 -LM +LM -LM +LM

IL-15 IL-18 2 1.5 1.5 WT 1 WT 1 KO KO 0.5 0.5 0 0 -LM +LM -LM +LM

FAS-L iNOS 2 2.5 2 1.5 WT 1.5 WT KO 1 1 KO 0.5 0.5 0 0 -LM +LM -LM +LM Sonoda_FigS14

WT STAT-1 KO

A

4 60000 30 50000 25 3 40000 20 2 30000 15 20000 10 1 10000 5 0 0 0

B 14 2 3 12 1.5 10 2 8 1 6 1 4 0.5 2 0 0 0

Sonoda_FigS15

Mac-1 FcγRIII/II F4/80 Gr-1

PGC1β+/+

PGC1β-/- Sonoda_FigS16

arginase NDG2 8 7 7 6

6 5 5 4 4 3 3 2 2 1 1 0 0

ATP5b IDH3A 1.8 2 1.6 1.8 1.6 1.4 1.4 1.2 1.2 1 1 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0

Aco2 CytC 1.8 3 1.6 2.5 1.4 1.2 2 1 1.5 0.8 0.6 1 0.4 0.5 0.2 0 0

Coq7 ATP5g3 1.6 2 1.8 1.4 1.6 1.2 1.4 1 1.2 0.8 1 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0 0

WT ERRα KO PGC-1β KO Sonoda_FigS17

# of genes Gene Ontology Term IFN-γ IL-4

Mitochondrion 94 104 Generation of Precursor Metabolites and Energy 65 75 Activity 56 59 Mitochondrial Membrane 56 52 Electron Transport 43 43 Mitochondrial Inner Membrane 50 48 Inner Membrane 51 48 Primary Active Transporter Activity 42 55 Monovalent Inorganic Cation Transporter Activity 41 57 Hydrogen Activity 41 57 Mitochondrial 16 17 Oxidative Phosphorylation 23 24 Tricarboxylic Acid Cycle 16 15 p values: <1E-10 Table S1. List of genes whose expression is significantly higher in WT cells than ERRa-/- cells in both IFN-g-treated and IL-4 treated groups. fold Difference fold Difference wt_value wt_value p.value p.value Affymetrix_ID gene_symbol IFNg IL4 IFNg IL4 IFNg IL4 function cellular location Gene Title 1424364_a_at 1110020P15Rik 1.2834259 1.36604026 11 12 0.011 0.0004 oxphos mitochondria RIKEN cDNA 1110020P15 gene 1434341_x_at 1110020P15Rik 1.29235283 1.39474367 8.1 9.4 0.00045 0.00066 oxphos mitochondria RIKEN cDNA 1110020P15 gene 1418814_s_at 2410011G03Rik 1.17283495 1.41421356 9.2 11 0.002 0.0046 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 1433513_x_at 2410011G03Rik 1.25701337 1.35660433 10 10 0.0047 0.0038 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 1455806_x_at 2410011G03Rik 1.26575659 1.38510947 10 11 0.0027 0.0085 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 1423111_at Atp5a1 1.2834259 1.1974787 12 13 0.012 0.022 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit, isoform 1 1416829_at Atp5b 1.32868581 1.40444488 12 13 0.0081 0.00091 oxphos mitochondria ATP synthase, H+ transporting mitochondrial F1 complex, beta subunit 1416058_s_at Atp5c1 1.23114441 1.27456063 11 12 0.02 0.0074 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 1423716_s_at Atp5d 1.24833055 1.24833055 10 11 0.025 0.0062 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit 1454661_at Atp5g3 1.31950791 1.2834259 12 13 0.00027 0.000057 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c (subunit 9), isoform 3 1423676_at Atp5h 1.13288389 1.13288389 11 12 0.043 0.0035 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d 1416143_at Atp5j 1.17283495 1.14869835 11 12 0.032 0.033 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F 1422525_at Atp5k 1.18099266 1.18920712 11 12 0.047 0.0065 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F1F0 complex, subunit e 1450640_x_at Atp5k 1.18099266 1.16473359 11 12 0.023 0.0057 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F1F0 complex, subunit e 1416278_a_at Atp5o 1.36604026 1.52625921 10 8.5 0.00011 0.021 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit 1437164_x_at Atp5o 1.18099266 1.40444488 7 11 0.031 0.0071 oxphos mitochondria ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit 1416665_at Coq7 1.62450479 1.54756499 7.8 9.8 0.00093 0.011 oxphos mitochondria demethyl-Q 7 1416902_a_at Cox5b 1.2397077 1.27456063 11 13 0.01 0.00038 oxphos mitochondria oxidase, subunit Vb 1435613_x_at Cox5b 1.22264028 1.30134186 12 12 0.018 0.0017 oxphos mitochondria , subunit Vb 1454716_x_at Cox5b 1.27456063 1.26575659 11 12 0.0078 0.00071 oxphos mitochondria cytochrome c oxidase, subunit Vb 1456588_x_at Cox5b 1.2834259 1.21419488 12 13 0.0095 0.00016 oxphos mitochondria cytochrome c oxidase, subunit Vb 1417417_a_at Cox6a1 1.17283495 1.11728714 12 13 0.025 0.016 oxphos mitochondria cytochrome c oxidase, subunit VI a, polypeptide 1 1416565_at Cox6b1 1.23114441 1.18920712 12 13 0.0019 0.0014 oxphos mitochondria cytochrome c oxidase, subunit VIb polypeptide 1 1436757_a_at Cox6b1 1.21419488 1.1974787 12 13 0.0048 0.0013 oxphos mitochondria cytochrome c oxidase, subunit VIb polypeptide 1 1416970_a_at Cox7a2 1.2397077 1.12505848 12 13 0.0037 0.037 oxphos mitochondria cytochrome c oxidase, subunit VIIa 2 1416112_at Cox8a 1.4240502 1.3103934 12 13 0.0016 0.00007 oxphos mitochondria cytochrome c oxidase, subunit VIIIa 1448222_x_at Cox8a 1.4439292 1.26575659 12 13 0.0031 0.000041 oxphos mitochondria cytochrome c oxidase, subunit VIIIa 1416604_at Cyc1 1.5691682 1.72907446 10 11 0.009 0.00014 oxphos mitochondria cytochrome c-1 1422483_a_at Cycs 1.40444488 1.2834259 11 13 0.0083 0.0013 oxphos mitochondria cytochrome c, somatic 1422484_at Cycs 1.35660433 1.45397252 8.5 10 0.044 0.0068 oxphos mitochondria cytochrome c, somatic 1417285_a_at Ndufa5 1.18920712 1.27456063 8.5 9.9 0.019 0.022 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5 1417286_at Ndufa5 1.32868581 1.22264028 9.2 10 0.00034 0.012 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5 1423692_at Ndufa8 1.13288389 1.14076372 10 11 0.037 0.016 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 8 1428322_a_at Ndufb10 1.17283495 1.20580783 9 10 0.022 0.0048 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 10 1416834_x_at Ndufb2 1.22264028 1.25701337 9.2 10 0.04 0.023 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2 1416285_at Ndufc1 1.30134186 1.26575659 11 12 0.0013 0.0081 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1 1455036_s_at Ndufc2 1.12505848 1.16473359 11 12 0.05 0.0057 oxphos mitochondria NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2 1425143_a_at Ndufs1 1.27456063 1.30134186 8.9 9.9 0.028 0.0052 oxphos mitochondria NADH dehydrogenase (ubiquinone) Fe-S protein 1 1423737_at Ndufs3 1.16473359 1.20580783 9.9 12 0.042 0.0015 oxphos mitochondria NADH dehydrogenase (ubiquinone) Fe-S protein 3 1448959_at Ndufs4 1.12505848 1.12505848 8.9 10 0.036 0.021 oxphos mitochondria NADH dehydrogenase (ubiquinone) Fe-S protein 4 1424313_a_at Ndufs7 1.3103934 1.45397252 9.1 11 0.0051 0.00089 oxphos mitochondria NADH dehydrogenase (ubiquinone) Fe-S protein 7 1451312_at Ndufs7 1.31950791 1.53687518 9.9 10 0.0085 0.00061 oxphos mitochondria NADH dehydrogenase (ubiquinone) Fe-S protein 7 1415967_at Ndufv1 1.16473359 1.16473359 9.2 10 0.0071 0.027 oxphos mitochondria NADH dehydrogenase (ubiquinone) flavoprotein 1 1438159_x_at Ndufv2 1.18099266 1.27456063 9.5 11 0.0034 0.0037 oxphos mitochondria NADH dehydrogenase (ubiquinone) flavoprotein 2 1452692_a_at Ndufv2 1.17283495 1.34723358 9.8 11 0.019 0.0098 oxphos mitochondria NADH dehydrogenase (ubiquinone) flavoprotein 2 1450968_at Uqcrfs1 1.23114441 1.30134186 10 11 0.037 0.014 oxphos mitochondria ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 1452133_at Uqcrh 1.14076372 1.17283495 11 12 0.017 0.001 oxphos mitochondria ubiquinol-cytochrome c reductase hinge protein 1436934_s_at Aco2 1.32868581 1.48452357 8.8 10 0.01 0.00067 TCA cycle mitochondria 2, mitochondrial 1451002_at Aco2 1.40444488 1.4640857 11 12 0.011 0.00055 TCA cycle mitochondria aconitase 2, mitochondrial 1426264_at Dlat 1.20580783 1.30134186 7.6 9 0.012 0.00031 TCA cycle mitochondria dihydrolipoamide S-acetyltransferase (E2 component of complex) 1426265_x_at Dlat 1.36604026 1.31950791 7.8 8.7 0.0016 0.00088 TCA cycle mitochondria dihydrolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase complex) 1423710_at Dlst 1.20580783 1.16473359 9.3 11 0.0025 0.045 TCA cycle mitochondria dihydrolipoamide S-succinyltransferase (E2 component of 2-oxo-glutarate complex) 1422500_at Idh3a 1.32868581 1.8276629 5.3 10 0.016 0.0011 TCA cycle mitochondria 3 (NAD+) alpha 1418885_a_at Idh3b 1.29235283 1.35660433 9.6 11 0.0075 0.002 TCA cycle mitochondria isocitrate dehydrogenase 3 (NAD+) beta 1418886_s_at Idh3b 1.3103934 1.30134186 9.8 11 0.035 0.011 TCA cycle mitochondria isocitrate dehydrogenase 3 (NAD+) beta 1416789_at Idh3g 1.10190512 1.15668818 9.8 10 0.025 0.044 TCA cycle mitochondria isocitrate dehydrogenase 3 (NAD+), gamma 1416478_a_at Mdh2 1.2834259 1.21419488 11 12 0.047 0.012 TCA cycle mitochondria 2, NAD (mitochondrial) 1451274_at Ogdh 1.20580783 1.23114441 9.1 10 0.044 0.0039 TCA cycle mitochondria oxoglutarate dehydrogenase (lipoamide) 1418560_at Pdha1 1.16473359 1.14869835 10 11 0.039 0.0026 TCA cycle mitochondria pyruvate dehydrogenase E1 alpha 1 1416090_at Pdhb 1.22264028 1.2397077 9.7 11 0.02 0.000088 TCA cycle mitochondria pyruvate dehydrogenase (lipoamide) beta 1426688_at Sdha 1.31950791 1.35660433 11 11 0.017 0.0044 TCA cycle mitochondria complex, subunit A, flavoprotein (Fp) 1426689_s_at Sdha 1.26575659 1.24833055 10 12 0.0054 0.0041 TCA cycle mitochondria succinate dehydrogenase complex, subunit A, flavoprotein (Fp) 1418005_at Sdhb 1.22264028 1.27456063 11 13 0.017 0.00062 TCA cycle mitochondria succinate dehydrogenase complex, subunit B, iron sulfur (Ip) 1435986_x_at Sdhc 1.14869835 1.24833055 9.9 11 0.00014 0.04 TCA cycle mitochondria succinate dehydrogenase complex, subunit C, integral membrane protein 1448630_a_at Sdhc 1.21419488 1.18920712 9.8 11 0.028 0.035 TCA cycle mitochondria succinate dehydrogenase complex, subunit C, integral membrane protein 1428235_at Sdhd 1.26575659 1.38510947 11 12 0.0063 0.00031 TCA cycle mitochondria succinate dehydrogenase complex, subunit D, integral membrane protein 1415891_at Suclg1 1.14076372 1.12505848 9.3 10 0.0026 0.04 TCA cycle mitochondria succinate-CoA , GDP-forming, alpha subunit 1460635_at Fastk 1.22264028 1.4640857 7.9 9.3 0.0024 0.000021 apoptosis mitochondria Fas-activated serine/threonine kinase 1439410_x_at D11Ertd333e 1.20580783 1.18920712 11 13 0.036 0.0025 carrier mitochondria DNA segment, Chr 11, ERATO Doi 333, expressed 1453111_a_at D11Ertd333e 1.18099266 1.26575659 9.2 10 0.021 0.015 carrier mitochondria DNA segment, Chr 11, ERATO Doi 333, expressed 1426522_at Hadhb 1.22264028 1.23114441 9.7 11 0.039 0.0062 FAO mitochondria Mitochondrial trifunctional protein, beta subunit 1437192_x_at Vdac1 1.21419488 1.17283495 11 12 0.017 0.0059 membrane channel mitochondria voltage-dependent anion channel 1 1448131_at Mfn2 1.11728714 1.2397077 7.4 8.6 0.031 0.012 mitochondria fusion mitochondria mitofusin 2 1417591_at Ptges2 1.30134186 1.3103934 7.5 8.9 0.012 0.00083 prostaglandin synthase mitochondria prostaglandin E synthase 2 1416940_at Ppif 1.4240502 1.4640857 7.8 8.9 0.0038 0.0025 protein folding mitochondria peptidylprolyl F (cyclophilin F) 1452048_at Mrpl12 1.34723358 1.34723358 8.6 10 0.012 0.0014 protein synthesis mitochondria mitochondrial L12 1429054_at Mrpl47 1.29235283 1.45397252 6.9 8.8 0.0082 0.0056 protein synthesis mitochondria mitochondrial ribosomal protein L47 1429453_a_at Mrpl55 1.24833055 1.24833055 7.7 9.3 0.02 0.018 protein synthesis mitochondria mitochondrial ribosomal protein L55 1421875_a_at Mrps23 1.10190512 1.12505848 8.4 9.5 0.0072 0.0079 protein synthesis mitochondria mitochondrial ribosomal protein S23 1452111_at Mrps35 1.14869835 1.2397077 8 9.1 0.0063 0.033 protein synthesis mitochondria mitochondrial ribosomal protein S35 1428068_at 1110030L07Rik 1.25701337 1.24833055 9.7 11 0.019 0.0096 protein transport mitochondria sorting and assembly machinery component 50 homolog (S. cerevisiae) 1455800_x_at 1110030L07Rik 1.23114441 1.23114441 9.9 11 0.03 0.044 protein transport mitochondria sorting and assembly machinery component 50 homolog (S. cerevisiae) 1417499_at Timm13a 1.38510947 1.51571657 8.8 10 0.029 0.001 protein transport mitochondria of inner mitochondrial membrane 10 homolog (yeast) 1426256_at Timm17a 1.24833055 1.29235283 8.8 10 0.0015 0.0059 protein transport mitochondria translocase of inner mitochondrial membrane 17a 1417670_at Timm44 1.10190512 1.11728714 7.8 8.8 0.026 0.001 protein transport mitochondria translocase of inner mitochondrial membrane 44 1428087_at Dnm1l 1.17283495 1.11728714 9.3 9.9 0.002 0.018 signaling mitochondria dynamin 1-like 1426581_at Ptpmt1 1.2834259 1.26575659 9.8 11 0.013 0.0016 signaling mitochondria protein tyrosine phosphatase, mitochondrial 1 1437379_x_at Trap1 1.18920712 1.13288389 7.6 9.6 0.026 0.015 signaling mitochondria TNF receptor-associated protein 1, mRNA (cDNA clone MGC:28702 IMAGE:4242394) 1427997_at 1110007M04Rik 1.33792755 1.62450479 8.5 6.9 0.0036 0.04 unknown mitochondria RIKEN cDNA 1110007M04 gene 1428258_at 2010107E04Rik 1.2834259 1.18920712 9.9 11 0.0018 0.00013 unknown mitochondria RIKEN cDNA 2010107E04 gene 1449714_at 5730472N09Rik 1.14869835 1.20580783 8.1 8.6 0.0078 0.026 unknown mitochondria RIKEN cDNA 5730472N09 gene 1451504_at Chchd3 1.14076372 1.18099266 8.9 9.8 0.025 0.041 unknown mitochondria coiled-coil-helix-coiled-coil-helix domain containing 3 1416849_at D10Ertd214e 1.14076372 1.25701337 7.4 9.1 0.03 0.022 unknown mitochondria DNA segment, Chr 10, ERATO Doi 214, expressed 1416850_s_at D10Ertd214e 1.10956947 1.26575659 8.8 10 0.012 0.024 unknown mitochondria DNA segment, Chr 10, ERATO Doi 214, expressed 1423651_at Hbld2 1.32868581 1.51571657 8.6 9.6 0.03 0.00031 unknown mitochondria HESB like domain containing 2 1423652_at Hbld2 1.1974787 1.33792755 7.8 8.3 0.047 0.00065 unknown mitochondria HESB like domain containing 2 1433720_s_at Ndg2 5.27803164 9.84915531 8.3 9.9 0.00032 8.2E-07 unknown mitochondria Nur77 downstream gene 2 1436990_s_at Ndg2 4.59479342 6.96440451 7.7 9.1 1.9E-05 0.000046 unknown mitochondria Nur77 downstream gene 2 1448179_at Usmg5 1.15668818 1.12505848 9.7 11 0.045 0.00046 unknown mitochondria upregulated during skeletal muscle growth 5 1422627_a_at Mkks 1.12505848 1.31950791 8.5 9.4 0.044 0.034 protein folding centrosome McKusick-Kaufman syndrome protein 1424474_a_at Camkk2 1.17283495 1.14076372 8.3 8.6 0.05 0.034 signaling calcium/calmodulin-dependent protein kinase kinase 2, beta 1429763_at D530030D03Rik 1.17283495 1.25701337 9.5 11 0.0097 0.0037 unknown cytoplasm cornichon homolog 4 (Drosophila) 1417212_at 9530058B02Rik 1.26575659 1.2397077 7.2 7.7 0.03 0.01 unknown cytoplasm/nuclear RIKEN cDNA 9530058B02 gene 1416963_at Ubadc1 1.16473359 1.48452357 8.5 10 0.028 0.00044 unknown cytoplasm/nuclear ubiquitin associated domain containing 1 1460652_at Esrra 3.03143313 2.63901582 6.9 8.4 0.00028 0.0015 transcription nuclear Estrogen related receptor, alpha (Esrra), mRNA 1451132_at Pbxip1 1.23114441 1.27456063 8.7 9.4 0.027 0.035 transcription nuclear pre-B-cell leukemia transcription factor interacting protein 1 1450200_s_at Csf2rb1 1.39474367 1.2397077 11 11 0.00031 0.012 signaling plasma membrane colony stimulating factor 2 receptor, beta 1, low-affinity (granulocyte-macrophage) 1449360_at Csf2rb2 1.36604026 1.37554182 11 12 0.02 0.0024 signaling plasma membrane colony stimulating factor 2 receptor, beta 2, low-affinity (granulocyte-macrophage) 1428106_at 1300001I01Rik 1.48452357 1.8403753 9 9.8 0.017 0.00043 unknown unknown RIKEN cDNA 1300001I01 gene 1452626_a_at 1810014F10Rik 1.48452357 1.72907446 7.4 8.5 0.0051 0.0064 unknown unknown RIKEN cDNA 1810014F10 gene 1452342_at AU018552 1.10956947 1.14076372 8.3 7.5 0.00092 0.046 unknown unknown amyloid beta (A4) precursor protein-binding, family B, member 2 Functional annotation and subcellular location is based on www.affymetrix.com, www.ensembl.org or localization of GFP fusion proteins (Fig. S5). Table S2. List of genes whose expression is significantly altered (>5 fold) by IFN-g in WT macrophages ProbeSet Avg Ratio UniGene ID Gene Title Gene Symbol 1418652_at 307.97 Mm.766 chemokine (C-X-C motif) ligand 9 Cxcl9 1424923_at 134.05 Mm.264709 serine (or cysteine) proteinase inhibitor, clade A, member 3G Serpina3g 1420549_at 132 Mm.250 guanylate nucleotide binding protein 1 Gbp1 1450446_a_at 113.16 Mm.130 suppressor of cytokine signaling 1 Socs1 1425002_at 74.09 Mm.69553 cDNA sequence BC010462 BC010462 1448562_at 70.74 Mm.4610 uridine phosphorylase 1 Upp1 1420393_at 42.22 Mm.2893 nitric oxide synthase 2, inducible, macrophage Nos2 1421057_at 31.27 Mm.272258 deoxyribonuclease 1-like 3 Dnase1l3 1450495_a_at 25.2 Mm.8217 killer cell lectin-like receptor subfamily K, member 1 Klrk1 1419721_at 24.82 Mm.77690 G protein-coupled receptor 109B Gpr109b 1425294_at 24.82 Mm.179812 SLAM family member 8 Slamf8 1418030_at 21.61 Mm.268798 solute carrier organic anion transporter family, member 3a1 Slco3a1 1419697_at 21.11 Mm.131723 chemokine (C-X-C motif) ligand 11 Cxcl11 1418930_at 18.81 Mm.877 chemokine (C-X-C motif) ligand 10 Cxcl10 1418776_at 16.63 --- RIKEN cDNA 5830443L24 gene 5830443L24Rik 1419042_at 16.37 Mm.261140 expressed sequence AW111922 AW111922 1430005_a_at 16 Mm.159219 RIKEN cDNA 4933430F08 gene 4933430F08Rik 1448918_at 15.28 Mm.268798 solute carrier organic anion transporter family, member 3a1 Slco3a1 1419282_at 15.04 Mm.867 chemokine (C-C motif) ligand 12 Ccl12 1425156_at 15.04 Mm.45740 RIKEN cDNA 9830147J24 gene 9830147J24Rik 1419043_a_at 14.59 Mm.326506 expressed sequence AW111922 AW111922 1449227_at 14.04 Mm.30824 cholesterol 25-hydroxylase Ch25h 1436836_x_at 13.82 Mm.275555 calponin 3, acidic Cnn3 1416576_at 12.6 Mm.3468 suppressor of cytokine signaling 3 Socs3 1451611_at 12.41 Mm.274810 HRAS like suppressor 3 Hrasls3 1438676_at 11.85 Mm.354723 expressed sequence AI595338 AI595338 1455570_x_at 11.31 Mm.275555 calponin 3, acidic Cnn3 1422527_at 10.97 Mm.16373 histocompatibility 2, class II, DMa H2-DMa 1418240_at 10.56 Mm.24038 guanylate nucleotide binding protein 2 Gbp2 1425394_at 10.39 Mm.329462 cDNA sequence BC023105 BC023105 1448436_a_at 10.39 Mm.105218 interferon regulatory factor 1 Irf1 1455899_x_at 10.31 Mm.3468 suppressor of cytokine signaling 3 Socs3 1456212_x_at 9.85 Mm.3468 suppressor of cytokine signaling 3 Socs3 1436759_x_at 9.77 Mm.275555 calponin 3, acidic Cnn3 1460415_a_at 9.33 Mm.271833 tumor necrosis factor receptor superfamily, member 5 Tnfrsf5 1449009_at 8.71 Mm.338891 T-cell specific GTPase Tgtp 1438942_x_at 8.57 Mm.330731 2, C polypeptide Tgm2 1421211_a_at 8.44 Mm.249560 class II transactivator C2ta 1418392_a_at 8.19 Mm.1909 guanylate nucleotide binding protein 4 Gbp4 1421228_at 8.19 Mm.341574 chemokine (C-C motif) ligand 7 Ccl7 1417141_at 8.12 Mm.33902 interferon gamma induced GTPase Igtp 1426724_at 8.06 Mm.275555 calponin 3, acidic Cnn3 1451064_a_at 7.88 Mm.289936 phosphoserine aminotransferase 1 Psat1 1451721_a_at 7.82 Mm.254067 histocompatibility 2, class II antigen A, beta 1 H2-Ab1 1420380_at 7.76 Mm.290320 chemokine (C-C motif) ligand 2 Ccl2 1417262_at 7.58 Mm.292547 prostaglandin-endoperoxide synthase 2 Ptgs2 1434380_at 7.52 Mm.254851 Diabetic nephropathy-related gene 1 mRNA, partial sequence --- 1449473_s_at 7.52 Mm.271833 tumor necrosis factor receptor superfamily, member 5 Tnfrsf5 1424041_s_at 7.24 Mm.347015 complement component 1, s subcomponent C1s 1451340_at 7.13 Mm.34316 AT rich interactive domain 5A (Mrf1 like) Arid5a 1425477_x_at 7.07 Mm.254067 histocompatibility 2, class II antigen A, beta 1 H2-Ab1 1452431_s_at 6.91 Mm.235338 histocompatibility 2, class II antigen A, alpha H2-Aa 1454607_s_at 6.91 Mm.289936 phosphoserine aminotransferase 1 Psat1 1419470_at 6.81 Mm.139192 guanine nucleotide binding protein, beta 4 Gnb4 1451335_at 6.81 Mm.34609 placenta-specific 8 Plac8 1419469_at 6.65 Mm.139192 guanine nucleotide binding protein, beta 4 Gnb4 1419202_at 6.6 Mm.12965 cystatin F (leukocystatin) Cst7 1421210_at 6.6 Mm.249560 class II transactivator C2ta 1419714_at 6.35 Mm.245363 programmed cell death 1 ligand 1 Pdcd1lg1 1434813_x_at 6.25 Mm.38433 tryptophanyl-tRNA synthetase Wars 1435906_x_at 6.25 Mm.24038 guanylate nucleotide binding protein 2 Gbp2 1437832_x_at 5.88 Mm.38433 tryptophanyl-tRNA synthetase Wars 1415694_at 5.83 Mm.38433 tryptophanyl-tRNA synthetase Wars 1417164_at 5.7 Mm.266191 dual specificity phosphatase 10 Dusp10 1450648_s_at 5.61 Mm.254067 histocompatibility 2, class II antigen A, beta 1 H2-Ab1 1417025_at 5.57 Mm.22564 histocompatibility 2, class II antigen E beta H2-Eb1 1449945_at 5.57 Mm.35750 peroxisome proliferative activated receptor, gamma, coactivator 1 beta Ppargc1b 1417240_at 5.53 Mm.282303 zyxin Zyx 1451544_at 5.44 Mm.296902 TAP binding protein-like Tapbpl 1425106_a_at 5.4 Mm.38433 tryptophanyl-tRNA synthetase Wars 1448681_at 5.4 Mm.200196 interleukin 15 receptor, alpha chain Il15ra 1423614_at 5.36 Mm.348765 RIKEN cDNA E430036I04 gene E430036I04Rik 1426004_a_at 5.36 Mm.330731 transglutaminase 2, C polypeptide Tgm2 1449454_at 5.36 Mm.246332 bone marrow stromal cell antigen 1 Bst1 1451798_at 5.24 Mm.882 interleukin 1 receptor antagonist Il1rn 1419684_at 5.2 Mm.42029 chemokine (C-C motif) ligand 8 Ccl8 1417300_at 5.16 Mm.287187 sphingomyelin phosphodiesterase, acid-like 3B Smpdl3b 1423017_a_at 5.12 Mm.882 interleukin 1 receptor antagonist Il1rn 1450350_a_at 5.08 Mm.103560 Jun dimerization protein 2 Jundm2 1451330_a_at 5.08 Mm.296202 inositol polyphosphate-5-phosphatase B Inpp5b 1425519_a_at 5.04 Mm.276499 Ia-associated invariant chain Ii 1418480_at -5 Mm.293614 chemokine (C-X-C motif) ligand 7 Cxcl7 1421839_at -5 Mm.277376 ATP-binding cassette, sub-family A (ABC1), member 1 Abca1 1454699_at -5.04 Mm.276226 sestrin 1 Sesn1 1438931_s_at -5.12 Mm.276226 sestrin 1 Sesn1 1420398_at -5.2 Mm.253927 regulator of G-protein signaling 18 Rgs18 1428301_at -5.28 Mm.277357 RIKEN cDNA 2610042L04 gene 2610042L04Rik 1420928_at -5.49 Mm.149029 beta galactoside alpha 2,6 sialyltransferase 1 St6gal1 1417597_at -5.53 Mm.255003 CD28 antigen Cd28 1455826_a_at -5.57 Mm.24044 beta-site APP cleaving 1 Bace1 1416298_at -5.7 Mm.4406 matrix metalloproteinase 9 Mmp9 1449145_a_at -5.97 Mm.28278 caveolin, caveolae protein 1 Cav1 1455220_at -6.3 Mm.222723 frequently rearranged in advanced T-cell lymphomas 2 Frat2 1417061_at -6.55 Mm.28756 solute carrier family 40 (iron-regulated transporter), member 1 Slc40a1 1424998_at -6.75 Mm.210497 EGF-like module containing, mucin-like, hormone receptor-like sequence 4 Emr4 1448566_at -6.91 Mm.28756 solute carrier family 40 (iron-regulated transporter), member 1 Slc40a1 1449402_at -6.91 Mm.44827 carbohydrate (N-acetylglucosamino) sulfotransferase 7 Chst7 1454897_at -7.07 --- RIKEN cDNA 6330509M05 gene 6330509M05Rik 1424265_at -7.41 Mm.24887 N-acetylneuraminate pyruvate Npl 1448710_at -8 Mm.1401 chemokine (C-X-C motif) receptor 4 Cxcr4 1450392_at -8.19 Mm.277376 ATP-binding cassette, sub-family A (ABC1), member 1 Abca1 1453571_at -8.84 Mm.295397 DEP domain containing 6 Depdc6 1437025_at -8.91 Mm.255003 CD28 antigen Cd28 1423436_at -9.77 Mm.14719 glutathione S-, alpha 3 Gsta3 1451563_at -10.31 Mm.210497 EGF-like module containing, mucin-like, hormone receptor-like sequence 4 Emr4 1451348_at -14.59 Mm.295397 DEP domain containing 6 Depdc6 Table S3. List of genes whose expression is significantly altered (>5 fold) by IL-4 in WT macrophages ProbeSet Avg Ratio UniGene ID Gene Title Gene Symbol 1419549_at 2178.15 Mm.154144 arginase 1, liver Arg1 1449015_at 877.82 Mm.33772 resistin like alpha Retnla 1425295_at 291.81 Mm.153688 eosinophil-associated, ribonuclease A family, member 11 Ear11 1450488_at 237.02 Mm.31505 chemokine (C-C motif) ligand 24 Ccl24 1425145_at 158.8 Mm.289824 interleukin 1 receptor-like 1 Il1rl1 1419300_at 105.58 Mm.3464 FMS-like tyrosine kinase 1 Flt1 1419192_at 96.26 Mm.347426 interleukin 4 induced 1 Il4i1 1421173_at 76.99 Mm.4677 interferon regulatory factor 4 Irf4 1438467_at 66 Mm.222465 macrophage galactose N-acetyl-galactosamine specific lectin 2 Mgl2 1421456_at 63.02 Mm.281452 purinergic receptor P2Y, G-protein coupled 1 P2ry1 1448261_at 54.86 Mm.35605 cadherin 1 Cdh1 1425386_at 52.39 Mm.72179 RIKEN cDNA 4833422F24 gene 4833422F24Rik 1421739_a_at 47.03 Mm.2918 megakaryocyte-associated tyrosine kinase Matk 1419128_at 41.9 Mm.22378 integrin alpha X Itgax 1451924_a_at 41.26 Mm.14543 endothelin 1 Edn1 1449022_at 37.33 Mm.331129 nestin Nes 1432329_a_at 33.26 Mm.2918 megakaryocyte-associated tyrosine kinase Matk 1427683_at 32.5 Mm.290421 early growth response 2 Egr2 1436448_a_at 31.51 Mm.275434 prostaglandin-endoperoxide synthase 1 Ptgs1 1425451_s_at 30.09 Mm.4571 chitinase 3-like 3 Chi3l3 1417389_at 29.63 Mm.297976 glypican 1 Gpc1 1426008_a_at 28.07 Mm.4676 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 Slc7a2 1451756_at 27.64 Mm.3464 FMS-like tyrosine kinase 1 Flt1 1452473_at 27.01 Mm.41984 RIKEN cDNA E130201N16 gene E130201N16Rik 1427682_a_at 24.07 Mm.290421 early growth response 2 Egr2 1428289_at 24.07 Mm.291595 basic transcription element binding protein 1 Bteb1 1422967_a_at 23.88 Mm.28683 transferrin receptor Tfrc 1419764_at 23.34 Mm.4571 chitinase 3-like 3 Chi3l3 1456341_a_at 23.34 Mm.291595 basic transcription element binding protein 1 Bteb1 1418507_s_at 22.8 --- RIKEN cDNA D130043N08 gene D130043N08Rik 1454037_a_at 22.11 Mm.3464 FMS-like tyrosine kinase 1 Flt1 1421511_at 21.94 Mm.87150 integrin beta 3 Itgb3 1418992_at 20.31 Mm.262589 coagulation factor X F10 1419605_at 20.16 Mm.252405 macrophage galactose N-acetyl-galactosamine specific lectin 1 Mgl1 1450703_at 19.4 Mm.4676 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 Slc7a2 1422648_at 18.95 Mm.4676 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 Slc7a2 1427306_at 17.82 Mm.350778 ryanodine receptor 1, skeletal muscle Ryr1 1418350_at 17.68 Mm.289681 diphtheria toxin receptor Dtr 1423414_at 17.28 Mm.275434 prostaglandin-endoperoxide synthase 1 Ptgs1 1450446_a_at 17.15 Mm.130 suppressor of cytokine signaling 1 Socs1 1424911_a_at 16.89 Mm.33351 lysozyme-like 4 Lyzl4 1418912_at 16.25 Mm.313938 plexin domain containing 2 Plxdc2 1450457_at 15.88 Mm.266871 Casitas B-lineage lymphoma Cbl 1418497_at 15.63 Mm.7995 fibroblast growth factor 13 Fgf13 1420407_at 15.51 Mm.20853 leukotriene B4 receptor 1 Ltb4r1 1450076_at 15.28 Mm.133623 RIKEN cDNA 4933411K20 gene 4933411K20Rik 1426562_a_at 14.36 Mm.43278 olfactomedin 1 Olfm1 1450290_at 14.15 Mm.116737 programmed cell death 1 ligand 2 Pdcd1lg2 1421002_at 13.72 Mm.208919 angiopoietin-like 2 Angptl2 1449109_at 13.72 Mm.291261 suppressor of cytokine signaling 2 Socs2 1418025_at 13.61 Mm.2436 basic helix-loop-helix domain containing, class B2 Bhlhb2 1421239_at 12.51 Mm.4364 interleukin 6 signal transducer Il6st 1451535_at 12.13 Mm.229334 interleukin 31 receptor A Il31ra 1418993_s_at 11.76 Mm.262589 coagulation factor X F10 1449305_at 11.31 Mm.262589 coagulation factor X F10 1421228_at 10.97 Mm.341574 chemokine (C-C motif) ligand 7 Ccl7 1422966_a_at 10.89 Mm.28683 transferrin receptor Tfrc 1418843_at 10.31 Mm.27801 solute carrier family 30 (zinc transporter), member 4 Slc30a4 1416034_at 9.85 Mm.29742 CD24a antigen Cd24a 1425784_a_at 9.85 Mm.43278 olfactomedin 1 Olfm1 1448182_a_at 9.77 Mm.29742 CD24a antigen Cd24a 1424402_at 9.19 Mm.270469 DNA segment, Chr 5, Brigham & Women's Genetics 0860 expressed D5Bwg0860e 1425273_s_at 8.91 Mm.246009 epithelial membrane protein 2 Emp2 1420923_at 8.44 Mm.242646 ubiquitin specific protease 9, X chromosome Usp9x 1426053_a_at 8.44 Mm.266215 xenotropic and polytropic retrovirus receptor 1 Xpr1 1421174_at 8.25 Mm.4677 interferon regulatory factor 4 Irf4 1425019_at 8.06 Mm.259170 UBX domain containing 4 Ubxd4 1455886_at 7.76 Mm.266871 Casitas B-lineage lymphoma Cbl 1450085_at 7.58 Mm.208919 angiopoietin-like 2 Angptl2 1425227_a_at 7.46 Mm.20869 ATPase, H+ transporting, lysosomal V0 subunit a isoform 1 Atp6v0a1 1428288_at 7.24 --- RIKEN cDNA 2310051E17 gene 2310051E17Rik 1420380_at 7.18 Mm.290320 chemokine (C-C motif) ligand 2 Ccl2 1424671_at 7.18 Mm.333798 pleckstrin homology domain containing, family F member 1 Plekhf1 1453076_at 7.13 Mm.6922 RIKEN cDNA 9130211I03 gene 9130211I03Rik 1435386_at 7.07 Mm.22339 Von Willebrand factor homolog Vwf 1456333_a_at 6.81 Mm.260183 Rho GTPase activating protein 6 Arhgap6 1439037_at 6.75 Mm.29644 RIKEN cDNA 2610007K22 gene 2610007K22Rik 1448724_at 6.75 Mm.4592 cytokine inducible SH2-containing protein Cish 1425836_a_at 6.7 Mm.15409 LIM-domain containing, protein kinase Limk1 1416052_at 6.65 Mm.287178 phosphoribosyl pyrophosphate synthetase 1 Prps1 1426574_a_at 6.55 Mm.44106 adducin 3 (gamma) Add3 1452292_at 6.4 Mm.39053 adaptor-related protein complex 2, beta 1 subunit Ap2b1 1417558_at 6.3 Mm.4848 Fyn proto-oncogene Fyn 1436763_a_at 6.3 Mm.291595 basic transcription element binding protein 1 Bteb1 1426622_a_at 6.25 Mm.293870 glutaminyl-peptide cyclotransferase (glutaminyl cyclase) Qpct 1449402_at 6.25 Mm.44827 carbohydrate (N-acetylglucosamino) sulfotransferase 7 Chst7 1455796_x_at 6.2 Mm.43278 olfactomedin 1 Olfm1 1416805_at 6.16 Mm.331088 RIKEN cDNA 1110032E23 gene 1110032E23Rik 1419202_at 6.16 Mm.12965 cystatin F (leukocystatin) Cst7 1448793_a_at 6.16 Mm.3815 syndecan 4 Sdc4 1452419_at 6.16 Mm.272077 RIKEN cDNA B130016L12 gene B130016L12Rik 1421967_at 6.11 Mm.200886 UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 5 B4galt5 1422135_at 6.02 Mm.42054 zinc finger protein 146 Zfp146 1422527_at 6.02 Mm.16373 histocompatibility 2, class II, locus DMa H2-DMa 1423522_at 6.02 Mm.1406 nucleoplasmin 3 Npm3 1450500_at 5.97 Mm.209150 kinase interacting with leukemia-associated gene (stathmin) Kist 1454070_a_at 5.97 Mm.121918 DDHD domain containing 1 Ddhd1 1420699_at 5.88 Mm.239516 C-type lectin, superfamily member 12 Clecsf12 1418932_at 5.83 Mm.136604 nuclear factor, interleukin 3, regulated Nfil3 1460295_s_at 5.74 Mm.4364 interleukin 6 signal transducer Il6st 1419748_at 5.66 Mm.295456 ATP-binding cassette, sub-family D (ALD), member 2 Abcd2 1421597_a_at 5.66 Mm.4816 homeo box, msh-like 3 Msx3 1436343_at 5.66 Mm.333388 chromodomain helicase DNA binding protein 4 Chd4 1423392_at 5.61 Mm.257765 chloride intracellular channel 4 (mitochondrial) Clic4 1422931_at 5.57 Mm.24684 fos-like antigen 2 Fosl2 1459923_at 5.53 Mm.296591 Hypothetical LOC328660 (LOC328660), mRNA --- 1421287_a_at 5.49 Mm.276652 platelet/endothelial cell adhesion molecule 1 Pecam1 1430388_a_at 5.44 Mm.280459 sulfatase 2 Sulf2 1452885_at 5.44 Mm.324474 RIKEN cDNA 2610510E10 gene 2610510E10Rik 1418892_at 5.36 Mm.27467 ras homolog gene family, member J Rhoj 1420710_at 5.36 Mm.4869 reticuloendotheliosis oncogene Rel 1420946_at 5.32 Mm.10141 alpha thalassemia/mental retardation syndrome X-linked homolog (human) Atrx 1425850_a_at 5.28 Mm.143818 NIMA (never in mitosis gene a)-related expressed kinase 6 Nek6 1435476_a_at 5.28 Mm.22119 Fc receptor, IgG, low affinity IIb Fcgr2b 1422868_s_at 5.2 Mm.45054 guanine deaminase Gda 1417704_a_at 5.12 Mm.260183 Rho GTPase activating protein 6 Arhgap6 1460521_a_at 5.12 Mm.196290 RIKEN cDNA 5830411E10 gene 5830411E10Rik 1416559_at 5.04 Mm.231400 RIKEN cDNA 1500003O22 gene 1500003O22Rik 1450082_s_at 5.04 Mm.155708 ets variant gene 5 Etv5 1448192_s_at 5 Mm.287178 phosphoribosyl pyrophosphate synthetase 1 Prps1 1421008_at -5 Mm.24045 RIKEN cDNA 2510004L01 gene 2510004L01Rik 1417926_at -5.04 Mm.21516 RIKEN cDNA 5830426I05 gene 5830426I05Rik 1452352_at -5.04 --- cytotoxic T lymphocyte-associated protein 2 beta Ctla2b 1431591_s_at -5.08 Mm.4950 interferon, alpha-inducible protein G1p2 1451426_at -5.08 Mm.271830 DNA segment, Chr 11, Lothar Hennighausen 2, expressed D11Lgp2e 1419108_at -5.12 Mm.254336 oligophrenin 1 Ophn1 1416700_at -5.16 Mm.46497 ras homolog gene family, member E Rhoe 1417910_at -5.16 Mm.4189 cyclin A2 Ccna2 1438676_at -5.16 Mm.354723 expressed sequence AI595338 AI595338 1424842_a_at -5.24 Mm.261134 Rho GTPase activating protein 24 Arhgap24 1448205_at -5.28 Mm.318364 cyclin B1 /// cyclin B1, related sequence 1 Ccnb1 /// Ccnb1-rs1 1435454_a_at -5.36 Mm.89417 cDNA sequence BC006779 BC006779 1449145_a_at -5.36 Mm.28278 caveolin, caveolae protein 1 Cav1 1416299_at -5.4 Mm.37801 Shc SH2-domain binding protein 1 Shcbp1 1420950_at -5.4 Mm.271578 zinc and ring finger 1 Znrf1 1422478_a_at -5.4 Mm.255026 acetyl-Coenzyme A synthetase 2 (ADP forming) Acas2 1452242_at -5.44 Mm.9916 RIKEN cDNA 1200008O12 gene 1200008O12Rik 1427327_at -5.49 Mm.347593 paired immunoglobin-like type 2 receptor alpha Pilra 1418611_at -5.57 Mm.2514 gene rich cluster, A gene Grca 1452515_a_at -5.66 Mm.100638 xylosyltransferase II Xylt2 1424278_a_at -5.7 Mm.8552 baculoviral IAP repeat-containing 5 Birc5 1419569_a_at -5.88 Mm.19029 interferon-stimulated protein Isg20 1430811_a_at -5.92 Mm.151315 cell division cycle associated 1 Cdca1 1416309_at -6.02 Mm.290015 nucleolar and spindle associated protein 1 Nusap1 1448228_at -6.06 Mm.172 lysyl oxidase Lox 1438322_x_at -6.16 Mm.343538 farnesyl diphosphate farnesyl transferase 1 Fdft1 1452408_at -6.16 Mm.262117 three prime repair exonuclease 1 Trex1 1449143_at -6.25 Mm.180157 RIKEN cDNA 5830458K16 gene 5830458K16Rik 1452179_at -6.3 Mm.286285 PHD finger protein 17 Phf17 1427102_at -6.65 Mm.38192 schlafen 4 Slfn4 1423775_s_at -6.7 Mm.227274 protein regulator of cytokinesis 1 Prc1 1418293_at -6.91 Mm.2036 interferon-induced protein with tetratricopeptide repeats 2 Ifit2 1455009_at -7.13 Mm.276736 carboxypeptidase D Cpd 1421009_at -7.24 Mm.24045 RIKEN cDNA 2510004L01 gene 2510004L01Rik 1419943_s_at -7.35 Mm.260114 cyclin B1 Ccnb1 1424339_at -7.35 Mm.95479 2'-5' oligoadenylate synthetase-like 1 Oasl1 1425374_at -7.46 Mm.204887 2'-5' oligoadenylate synthetase 3 Oas3 1450783_at -7.46 Mm.6718 interferon-induced protein with tetratricopeptide repeats 1 Ifit1 1424046_at -7.58 Mm.2185 budding uninhibited by benzimidazoles 1 homolog (S. cerevisiae) Bub1 1440865_at -7.7 Mm.276440 interferon induced transmembrane protein 6 Ifitm6 1452954_at -7.88 Mm.89830 ubiquitin-conjugating enzyme E2C Ube2c 1423555_a_at -8 Mm.30756 interferon-induced protein 44 Ifi44 1425062_at -8.06 Mm.255203 RIKEN cDNA A230020G22 gene A230020G22Rik 1416121_at -8.31 Mm.172 lysyl oxidase Lox 1448918_at -8.98 Mm.268798 solute carrier organic anion transporter family, member 3a1 Slco3a1 1427707_a_at -9.19 Mm.3988 Tal1 interrupting locus Sil 1420671_x_at -9.7 Mm.159648 membrane-spanning 4-domains, subfamily A, member 4C Ms4a4c 1452731_x_at -10.16 Mm.277357 RIKEN cDNA 2610042L04 gene 2610042L04Rik 1448728_a_at -10.72 Mm.247272 expressed sequence AA408868 AA408868 1449498_at -10.89 Mm.1856 macrophage receptor with collagenous structure Marco 1421304_at -11.23 Mm.4783 killer cell lectin-like receptor, subfamily A, member 2 Klra2 1437611_x_at -11.23 Mm.247651 kinesin family member 2C Kif2c 1416076_at -12.03 Mm.260114 cyclin B1 Ccnb1 1448191_at -12.22 Mm.16525 polo-like kinase 1 (Drosophila) Plk1 1448713_at -12.31 Mm.1550 signal transducer and activator of transcription 4 Stat4 1423463_a_at -13.2 Mm.252695 DNA segment, Chr 2, ERATO Doi 750, expressed D2Ertd750e 1416632_at -13.72 Mm.295754 malic enzyme, supernatant Mod1 1449025_at -14.25 Mm.353948 interferon-induced protein with tetratricopeptide repeats 3 --- 1460242_at -14.7 Mm.101591 decay accelerating factor 1 Daf1 1450291_s_at -15.76 Mm.159648 membrane-spanning 4-domains, subfamily A, member 4C Ms4a4c 1450920_at -16.89 Mm.22592 cyclin B2 Ccnb2 1418762_at -19.55 Mm.101591 decay accelerating factor 1 Daf1 1418612_at -19.7 Mm.10948 schlafen 1 Slfn1 1417483_at -24.44 Mm.247272 expressed sequence AA408868 AA408868 1438377_x_at -29.63 Mm.250738 solute carrier family 13 (Na-dependent dicarboxylate transporter), member 3 Slc13a3 1422953_at -32.25 --- formyl peptide receptor, related sequence 2 Fpr-rs2 1416560_at -32.75 Mm.250738 solute carrier family 13 (Na-dependent dicarboxylate transporter), member 3 Slc13a3 1450808_at -43.21 Mm.56951 formyl peptide receptor 1 Fpr1 1421463_at -64.49 Mm.157702 SIGLEC-like 1 Siglecl1

Table S4. Functional classification of t arget genes bound by ERR in mou______se macr_oph_____ages______GENE Description GENE Description Amino acid metabolism Csf2rb2 colony stimulating factor 2 receptor, beta 2, low-affinity Got2 glutamate oxaloacetate transaminase 2, mitochondrial (granulocyte-macrophage) Hmgcl 3-hydroxy-3-methylglutaryl-Coenzyme A lyase Mx1 myxovirus (influenza virus) resistance 1 Carbohydrate metabolism Tlr1 toll-like receptor 1 Man2c1 mannosidase, alpha, class 2C, member 1 Tlr5 toll-like receptor 5 Cell growth/migration/adhesion Lipid metabolism Islr immunoglobulin superfamily containing leucine-rich repeat Pafah1b3 platelet-activating factor acetylhydrolase, isoform 1b, alpha1 Itgax integrin alpha X subunit Rtn4 reticulon 4 Oxidative phosphorylation/TCA cycle Stoml2 stomatin (Epb7.2)-like 2 Atp5b ATP synthase, H+ transporting mitochondrial F1 complex, beta Chromosome biogenesis subunit Hist1h2bc histone 1, H2bc Atp5c1 ATP synthase, H+ transporting, mitochondrial F1 complex, Hist1h4b histone 1, H4b gamma polypeptide 1 Hist1h4d histone 1, H4d Atp5g2 ATP synthase, H+ transporting, mitochondrial F0 complex, Hist1h4m histone 1, H4m subunit c (subunit 9), isoform 2 Tacc2 transforming, acidic coiled-coil containing protein 2 Atp5g3 ATP synthase, H+ transporting, mitochondrial F0 complex, Tacc3 transforming, acidic coiled-coil containing protein 3 subunit c (subunit 9), isoform 3 DNA metabolism Atp5k ATP synthase, H+ transporting, mitochondrial F1F0 complex, Kin antigenic determinant of rec-A protein subunit e Mcm3ap minichromosome maintenance deficient 3 (S. cerevisiae) Cox5b cytochrome c oxidase, subunit Vb associated protein Cox7a2 cytochrome c oxidase, subunit VIIa 2 Pole3 polymerase (DNA directed), epsilon 3 (p17 subunit) Cox8a cytochrome c oxidase, subunit VIIIa Polq polymerase (DNA directed), theta Cycs cytochrome c, somatic Supv311 suppressor of var1, 3-like 1 (S. cerevisiae) Ndufa5 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5 Glycolysis Ndufa9 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 Gpi1 glucose phosphate isomerase 1 Ndufb4 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 4 Heme metabolism Ndufb5 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5 Cox10 COX10 homolog, cytochrome c oxidase assembly protein, Ndufs1 NADH dehydrogenase (ubiquinone) Fe-S protein 1 heme A: farnesyltransferase (yeast) Ndufs7 NADH dehydrogenase (ubiquinone) Fe-S protein 7 Ncb5or cytochrome b5 reductase 4 Sdha succinate dehydrogenase complex, subunit A, flavoprotein (Fp) Inflammatory response Sdhd succinate dehydrogenase complex, subunit D, integral Alox5ap arachidonate 5- activating protein membrane protein Mpal2 macrophage activation 2 like Suclg1 succinate-CoA ligase, GDP-forming, alpha subunit Prdx5 peroxiredoxin 5 Protein metabolism and modification Immune response Ahsa1 AHA1, activator of heat shock 90kDa protein ATPase homolog Ccl12 chemokine (C-C motif) ligand 12 1 (yeast) Cd6 CD6 antigen Birc6 baculoviral IAP repeat-containing 6 Bms11 BMS1-like, assembly protein (yeast) Usp52 ubiquitin specific peptidase 52 Cct7 chaperonin subunit 7 (eta) Xrn1 5'-3' exoribonuclease 1 Clgn calmegin Zfp36 zinc finger protein 36 Comtd1 catechol-O-methyltransferase domain containing 1 Signal transduction Coq7 demethyl-Q 7 Akt1 thymoma viral proto-oncogene 1 Dnajc17 DnaJ (Hsp40) homolog, subfamily C, member 17 Arhgef1 Rho guanine nucleotide exchange factor (GEF) 1 Eef1b2 eukaryotic 1 beta 2 Bmx BMX non-receptor tyrosine kinase Eif3s6 3, subunit 6 Casr calcium-sensing receptor Galnt12 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- Cerk ceramide kinase acetylgalactosaminyltransferase 12 Edg8 endothelial differentiation, sphingolipid G-protein-coupled Gfm2 G elongation factor, mitochondrial 2 receptor, 8 Hspa9a heat shock protein 9A Gnb2 guanine nucleotide binding protein, beta 2 Lnpep leucyl/cystinyl aminopeptidase Itgb3bp integrin beta 3 binding protein (beta3-endonexin) Mrpl11 mitochondrial ribosomal protein L11 Mgst3 microsomal glutathione S-transferase 3 Mrpl19 mitochondrial ribosomal protein L19 Olfr56 olfactory receptor 56 Mrpl47 mitochondrial ribosomal protein L47 Olfr315 olfactory receptor 315 Mprs18b mitochondrial ribosomal protein S18B Olfr1015 olfactory receptor 1015 Nek4 NIMA (never in mitosis gene a)-related expressed kinase 4 Plxna2 plexin A2 Pfdn5 prefoldin 5 Sphk2 sphingosine kinase 2 Pja2 praja 2, RING-H2 motif containing Steroid and drug metabolism Ppil3 peptidylprolyl isomerase (cyclophilin)-like 3 Sult4a1 sulfotransferase family 4A, member 1 Ppp3cc protein phosphatase 3, catalytic subunit, gamma isoform Ugt1a6 UDP glucuronosyltransferase 1 family, polypeptide A6 Prcp prolylcarboxypeptidase (angiotensinase C) Transcriptional regulator Prepl prolyl endopeptidase-like Asb5 ankyrin repeat and SOCs box-containing protein 5 Psma6 proteasome (prosome, macropain) subunit, alpha type 6 Asb15 ankyrin repeat and SOCS box-containing protein 15 Psmb1 proteasome (prosome, macropain) subunit, beta type 1 Atf2 activating transcription factor 2 Rpl7l1 ribosomal protein L7-like 1 Crsp3 required for Sp1 transcriptional activation, subunit 3 Rps14 ribosomal protein S14 Esrra estrogen related receptor, alpha Sec11l1 Sec11-like 1 (S. cerevisiae) Gabpa GA repeat binding protein, alpha Trim30 tripartite motif protein 30 Gabpb2 GA repeat binding protein, beta 2 Trp53rk Trp53 regulating kinase Med4 mediator of RNA polymerase II transcription, subunit 4 Zfyve19 zinc finger, FYVE domain containing 19 homolog (yeast) RNA metabolism and processing Polrj2 polymerase (RNA) II (DNA directed) polypeptide J Dhx38 DEAH (Asp-Glu-Ala-His) box polypeptide 38 Ppp1r10 protein phosphatase 1, regulatory subunit 10 Exosc4 exosome component 4 Rnpc2 RNA-binding region (RNP1, RRM) containing 2 Grsf1 G-rich RNA sequence binding factor 1 Rxrb retinoid X receptor beta Phf5a PHD finger protein 5A Smarca2 SWI/SNF related, matrix associated, dependent regulator Snrpe small nuclear ribonucleoprotein E of chromatin, subfamily a, member 2 Ttc14 tetratricopeptide repeat domain 14 Smarca5 SWI/SNF related, matrix associated, actin dependent regulator Txnl4b thioredoxin-like 4B of chromatin, subfamily a, member 5 Supt7l suppressor of Ty 7 (S. cerevisiae)-like Rab21 RAB21, member RAS oncogene family Taf6 TAF6 RNA polymerase II, TATA box binding protein (TBP)- Rhcg Rhesus blood group-associated C glycoprotein associated factor Sec22l2 SEC22 vesicle trafficking protein-like 2 (S. cerevisiae) Tbp TATA box binding protein Slc4a1ap solute carrier family 4 (anion exchanger), member 1, adaptor Tead3 TEA domain family member 3 protein Tfb2m transcription factor B2, mitochondrial Slc41a3 solute carrier family 41, member 3 Whsc2 Wolf-Hirschhorn syndrome candidate 2 (human) Slc9a1 solute carrier family 9 (sodium/hydrogen exchanger), member Zpf142 zinc finger protein 142 1 Zfp143 zinc finger protein 143 Slc35b1 solute carrier family 35, member B1 Transport Slc39a7 solute carrier family 39 (zinc transporter), member 7 Abcb8 ATP-binding cassette, sub-family B (MDR/TAP), member 8 Timm8b translocase of inner mitochondrial membrane 8 homolog b Accn5 amiloride-sensitive cation channel 5, intestinal (yeast) Ap1g2 adaptor protein complex AP-1, gamma 2 subunit Timm10 translocase of inner mitochondrial membrane 10 homolog Atp2b2 ATPase, Ca++ transporting, plasma membrane 2 (yeast) Exoc3 exocyst complex component 3 Trappc3 trafficking protein particle complex 3 Gosr1 golgi SNAP receptor complex member 1 Vps28 vacuolar protein sorting 28 (yeast) Nup54 54 Rab2b RAB2B, member RAS oncogene family

______Genes without an assigned function at this level of analysis: 0610011N22Rik; 0610038D11Rik; 0610039G24Rik; 1110002N22Rik; 1110020P15Rik; 1500034E06Rik; 1810003N24Rik; 1810026J23Rik; 2310015N07Rik; 2610019P18Rik; 2610044O15Rik; 3100002L24Rik; 3110005O21Rik; 4632434I11Rik; 4930506M07Rik; 4930583K01Rik; 4933414I15Rik; 4933430I17; 4933434G05Rik; 5730427N09Rik; 5730589K01Rik; 9430023L20Rik; 9630058J23Rik; AA407526; A130042E20Rik; Acp2; AI413782; AI553587; Atxn10; BC019806; BC020077; BC051227; C530044N13Rik; Cd300lf; Chordc1; Cln8; Dock7; Dock11; D930001I22Rik; Dscr5; Gdpd5; Grwd1; Hbld2; Hdhd2; Hdhd3; Mbd6; Nsfl1c; Rab11fip4; Rfn187; Sacm1l; Sepm; Sh2d4b; Sh3rf2; Spata11; Theg; Tpr; Trim31; Ttc5; Unc93b; Yipf2; Zcchc14; Zcsl2; Zfp353; Zfp655; Zmat5.

In the case that one locus could be assigned to two distinct genes, both genes were included in the analysis.

Table S5. Validation of ERRa target promoters by standard ChIP. Chrom_Position_UCSC_AssMay2004 RefSeq UniGene_Symbol UniGene_Name pValue Enrichment chr13:70800053-70801053 NM_024201/NM_023281 0610011N22Rik/Sdha RIKEN cDNA 0610011N22 gene/succinate dehydrogenase complex, subunit A, flavoprotein (Fp) 0.001203774 9 chr15:81958662-81959662 NM_080633 Aco2 aconitase 2, mitochondrial 0.699189796 9.6 chr12:82600714-82601714 NM_146036/NM_134044 Ahsa1/AI413782 AHA1, activator of heat shock 90kDa protein ATPase homolog 1 (yeast)/expressed sequence AI413782 0.0080124 2 chr6:114442551-114443551 NM_009723 Atp2b2 ATPase, Ca++ transporting, plasma membrane 2 0.006305977 2 chr10:128210031-128211031 NM_016774 Atp5b ATP synthase, H+ transporting mitochondrial F1 complex, beta subunit 4.3121E-07 10 chr10:80038921-80039921 NM_025313 Atp5d ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit 0.028456306 3 chr11:95746527-95747527 NM_007506 Atp5g1 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c (subunit 9), isoform 1 0.019997261 2.1 chr2:73805260-73806260 NM_175015 Atp5g3 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c (subunit 9), isoform 3 1.85205E-11 17 chr5:105881849-105882849 NM_007507 Atp5k ATP synthase, H+ transporting, mitochondrial F1F0 complex, subunit e 0.00546451 4.1 chr7:105829855-105830855 NM_009940 Coq7 demethyl-Q 7 4.00742E-05 3.1 chr11:63691762-63692762 NM_178379 Cox10 COX10 homolog, cytochrome c oxidase assembly protein, heme A: farnesyltransferase (yeast) 0.009160864 2.3 chr19:6930756-6931756 NM_007750 Cox8a cytochrome c oxidase, subunit VIIIa 2.11017E-05 2.2 chr15:78631963-78632963 NM_007781 Csf2rb2 colony stimulating factor 2 receptor, beta 2, low-affinity (granulocyte-macrophage) 0.003919295 2 chr6:50516188-50517188 NM_007808 Cycs cytochrome c, somatic 0.000673527 2 chr19:6634996-6635996 NM_007953 Esrra estrogen related receptor, alpha 1.46152E-05 13 chr19:6634996-6635996 NM_007953 Esrra estrogen related receptor, alpha 1.46152E-05 14 chr16:85216950-85217950 NM_008065 Gabpa GA repeat binding protein, alpha 0.000109993 3.13 chr3:95212286-95213286 NM_172512 Gabpb2 GA repeat binding protein, beta 2 0.002860528 2 chr7:22644605-22645605 NM_008155 Gpi1 glucose phosphate isomerase 1 0.005960198 2 chr9:54794320-54795320 NM_029573 IDH3A isocitrate dehydrogenase 3 (NAD+) alpha 0.209594398 2.5 chr10:87611773-87612773 NM_010512 Igf1 insulin-like growth factor 1 0.026616944 2.2 chr11:53412734-53413734 NM_176938 Irf1 interferon regulatory factor 1 0.01176262 2.1 chr3:100623121-100624121 NM_010763 Man1b mannosidase 1, beta 0.011753129 2.3 chr6:82193088-82194088 NM_026490 Mrpl19 mitochondrial ribosomal protein L19 0.006217368 2 chr6:11663067-11664067 NM_010886 Ndufa4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4 0.011614265 3 chr6:127480596-127481596 NM_025358 Ndufa9 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 0.003986939 2 chr3:32519625-32520625 NM_025316/NM_029017 Ndufb5/4833424P18Rik NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5/RIKEN cDNA 4833424P18 gene 7.1864E-05 3.3 chr10:80149579-80150579 NM_029272 Ndufs7 NADH dehydrogenase (ubiquinone) Fe-S protein 7 2.31617E-06 16 chr5:134434303-134435303 NM_011962/BC026751 Plod3/Znhit1 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3/zinc finger, HIT domain containing 1 0.012759192 2.2 chr16:22971524-22972524 NM_145480 Rfc4 replication factor C (activator 1) 4 0.024652706 2.4 chr4:139416772-139417772 NM_023374 Sdhb succinate dehydrogenase complex, subunit B, iron sulfur (Ip) 0.017019345 4.2 chr2:84720301-84721301 NM_013899 Timm13a translocase of inner mitochondrial membrane 13 homolog a (yeast) 1.67657E-05 3.4 chr9:50763957-50764957 NM_013897/NM_025848 Timm8b/Sdhd translocase of inner mitochondrial membrane 8 homolog b (yeast)/succinate dehydrogenase complex, subunit D, integral membrane protein 1.21109E-05 6.5 chr5:63566709-63567709 NM_030682 Tlr1 toll-like receptor 1 0.006737276 2.1 chr4:48765699-48766699 NM_145547/NM_178603 Zfp189/Mrpl50 zinc finger protein 189/mitochondrial ribosomal protein L50 0.012734374 2.2 Below the cut-off but positive in standard ChIP Table S6. Immune cell populations in the spleen at two days post infection. 2X104 c.f.u. was injected intravenously. The relative number of each sub-population is presented by mean ± SD (n=4-8). Note that KO mice show significantly increased T-lymphocyte sub-populations positive for the early activation marker CD69, correlating with increased Listeria burden in the spleen (* p<0.05). Naive LM infected WT KO WT KO DX5+ NK cells 4.6 ± 1.4% 3.4 ± 0.8 % 1.3 ± 0.3% 1.2 ± 0.3 % CD11c+CD11b+ DC cells 2.4 ± 0.2% 2.5 ± 0.6 % 5.2 ± 1.2% 5.1 ± 0.8 % CD11c+CD11b- DC cells 3.3 ± 0.4% 4.2 ± 2.4 % 5.9 ± 1.7% 4.9 ± 0.8% B220+ B cells 36.8 ± 2.6% 31.5 ± 11 % 46.9 ± 8.8% 47.4 ± 6.7% CD11b+CD11c-DX5-B220- Macrophages 2.4 ± 0.4% 2.7 ± 0.8% 5 ± 1.6% 4.9 ± 1% CD8+ T cells 13.6 ± 1.1 % 12.8 ± 4.5 % 8.1 ± 2 % 9.2 ± 1.5 % CD8+CD69+ 1.8 ± 0.2 % 1.7 ± 0.3 % 48.3 ± 6.3% 57.2 ± 8.2% * CD8+CD69+CD25+ 0.3 ± 0.1 % 0.2 ± 0.01 % 3.3 ± 0.7 % 3 ± 1% CD4+ T cells 19.9 ± 1.9 % 17.4 ± 4.9 % 22.2 ± 3.4% 24.1 ± 3.4 % CD4+CD69+ 8.5 ± 2.7 % 8.2 ± 1.7 % 44.4 ± 8.3 % 55.4 ± 5.3 %* CD4+CD69+CD25+ 3.2 ± 1 % 3.2 ± 0.8 % 6.4 ± 1.4 % 6.8 ± 1.3 %