Supplemental Informations

Microarray method

Total RNA was purified using nucleospin RNA L columns (Macherey Nagel, Hoerdt,

France) according to the manufacturer’s recommendations. cDNA synthesis and biotin labelling of cRNA were performed using 5 µg total RNA and according to One-Cycle Target

Labelling protocol (Affymetrix, Santa Clara, CA). cRNA were hybridized to 12 Mouse

Genome 430A GeneChips (1 mouse per chip) and analyzed using a GeneChip 3000 7G scanner and the GeneChip Operative Software v1.1.1 (Affymetrix) at the Expression core facility of the Institute for Biotherapy (Montpellier, France). CEL files were processed using the ChipInspector software (Genomatix, Munich, Germany). ChipInspector uses single probe expression levels as input and map to transcripts probes that uniquely display significant changes. The methods circumvent false negative resulting from low signal probes, annotation errors and errors due to the existence of alternative transcripts. Differentially expressed between the AL and MT groups at both time points were identified using a

SAM (Significance analysis of Microarrays) one class comparison with the following settings: false discovery rate of 0.5%; minimal probe coverage: 3; minimal fold change threshold of 1.5. Down and up-regulated genes from both datasets (CT4 and CT16) were mapped to the (GO) biological process terms and calculated as over- represented (z-score) relative to the expected number of regulated genes in each GO category.

Cluster 3.0 and Treeview were used to construct the heatmap of the subset of genes regulated in a time dependent manner in the tumor of mice with restricted access to food.

Legends to figures

Supplementary Figure S1: Mean body weight in pooled Exp I and Exp II on the day preceding tumor inoculation (A) or 21 days after tumor inoculation (B) in mice fed ad libitum

1 (AL) or on meal timing (MT), with normal diet (N) or fat diet (F).

Supplementary Figure S2: Plasma corticosterone and IGF rhythms 3 weeks after tumor inoculation in mice fed AL (dashed line) or on MT (solid line) with normal (left panels) or fat diet (right panels). Plasma corticosterone (upper row) and IGF (low row). Horizontal axis hatched and black rectangles indicate subjective light and dark spans of photoperiodic cycle, respectively.

2 Supplementary Tables

Table S1: Biological processes down-regulated by meal timing at CT4 in P03 tumors.

GO Term GO ID Total Observed Expected ZScore regulation of progression through cell cycle GO:0000074 361 11 1,05 9,87 response to unfolded GO:0006986 59 4 0,17 9,3 protein folding GO:0006457 185 7 0,54 8,9 cell cycle GO:0007049 642 12 1,86 7,61 mitosis GO:0007067 140 5 0,41 7,26 cell division GO:0051301 203 6 0,59 7,12 response to stress GO:0006950 711 9 2,06 4,96 response to biotic stimulus GO:0009607 204 4 0,59 4,47 regulation of transcription from RNA polymerase II promoter GO:0006357 348 4 1,01 3,02 metabolic process GO:0008152 5978 27 17,31 3

Table S2: Biological processes up-regulated by meal timing at CT4 in P03 tumors.

GO Term GO ID Total Observed Expected ZScore mitosis GO:0007067 140 5 0,36 7,79 organization and biogenesis GO:0007010 459 5 1,18 3,58 response to chemical stimulus GO:0042221 323 4 0,83 3,53 cell cycle GO:0007049 642 6 1,65 3,47 carbohydrate metabolic process GO:0005975 337 4 0,86 3,41

Table S3: Biological processes down-regulated by meal timing at CT16 in P03 tumors.

GO Term GO ID Total Observed Expected ZScore response to heat GO:0009408 25 4 0,13 10,7 response to unfolded protein GO:0006986 59 5 0,31 8,45 response to protein stimulus GO:0051789 59 5 0,31 8,45 response to temperature stimulus GO:0009266 41 4 0,22 8,18 myeloid cell differentiation GO:0030099 96 6 0,51 7,77 protein folding GO:0006457 185 8 0,97 7,18 immune system development GO:0002520 242 8 1,27 6,02 hemopoietic or lymphoid organ development GO:0048534 227 7 1,19 5,36 response to chemical stimulus GO:0042221 323 8 1,7 4,9 response to biotic stimulus GO:0009607 204 6 1,07 4,8 hemopoiesis GO:0030097 204 6 1,07 4,8 developmental process GO:0032502 2560 27 13,48 4,05 organ development GO:0048513 1215 16 6,4 3,97 response to stress GO:0006950 711 11 3,74 3,85 response to abiotic stimulus GO:0009628 141 4 0,74 3,81 anatomical structure development GO:0048856 1752 20 9,22 3,78 cell differentiation GO:0030154 1534 18 8,08 3,69 RNA splicing GO:0008380 147 4 0,77 3,69 immune system process GO:0002376 646 10 3,4 3,67 regulation of GO:0042981 411 7 2,16 3,34 metabolic process GO:0008152 5978 45 31,47 3,1 anatomical structure morphogenesis GO:0009653 999 12 5,26 3,05 system development GO:0048731 1500 16 7,9 3,05 RNA metabolic process GO:0016070 1899 19 10 3,05 protein targeting GO:0006605 190 4 1 3,03 embryonic development GO:0009790 362 6 1,91 3,01

3 Table S4: Biological processes up-regulated by meal timing at CT16 in P03 tumors.

GO Term GO ID Total Observed Expected ZScore mitosis GO:0007067 140 14 1,57 10,04 cell cycle GO:0007049 642 26 7,18 7,22 cytokinesis GO:0000910 28 4 0,31 6,63 immune system process GO:0002376 646 23 7,23 6,03 immune response GO:0006955 410 16 4,59 5,43 taxis GO:0042330 106 6 1,19 4,46 nucleosome assembly GO:0006334 53 4 0,59 4,46 chemotaxis GO:0006935 106 6 1,19 4,46 protein-DNA complex assembly GO:0065004 86 5 0,96 4,15 biopolymer metabolic process GO:0043283 3453 61 38,63 4,12 skeletal development GO:0001501 159 7 1,78 3,96 microtubule cytoskeleton organization and biogenesis GO:0000226 64 4 0,72 3,91 bone remodeling GO:0046849 95 5 1,06 3,85 microtubule-based process GO:0007017 168 7 1,88 3,78 chromatin assembly GO:0031497 67 4 0,75 3,78 response to external stimulus GO:0009605 438 13 4,9 3,73 cell activation GO:0001775 216 8 2,42 3,64 tissue remodeling GO:0048771 104 5 1,16 3,59 regulation of cellular process GO:0050794 2956 51 33,07 3,49 leukocyte activation GO:0045321 200 7 2,24 3,22 protein modification GO:0006464 1223 25 13,68 3,21 hemopoiesis GO:0030097 204 7 2,28 3,16 ossification GO:0001503 85 4 0,95 3,15 biomineral formation GO:0031214 86 4 0,96 3,12 microtubule-based movement GO:0007018 88 4 0,98 3,07 leukocyte differentiation GO:0002521 127 5 1,42 3,03 cellular developmental process GO:0048869 1534 29 17,16 3,03 cell differentiation GO:0030154 1534 29 17,16 3,03 biopolymer modification GO:0043412 1266 25 14,16 3,02 regulation of cell growth GO:0001558 90 4 1,01 3,01

4 Table S5: Genes down-regulated in P03 tumors at CT4 after meal timing.

Biological Process Symbol Gene name Coverage Fold change Cell cycle Pycard PYD and CARD domain containing 8 0.50 Cdkn2d -dependent inhibitor 2D (p19) 3 0.60 Cdca3 cell division cycle associated 3/tome-1 4 0.62 Ccng2 cyclin G2 11 0.62 Ccnb1 cyclin B1 8 0.62 Aurkb B 3 0.62 Tacc3 transforming. acidic coiled-coil containing protein 3 3 0.62 Cdc20 cell division cycle 20 5 0.62 polo-like kinase 1 4 0.63 Ccna2 cyclin A2 6 0.64 Aspm asp (abnormal spindle)-like. microcephaly associated 5 0.65 Racgap1 Rac GTPase-activating protein 1 5 0.65 Cell organization Prg4 proteoglycan 4 5 0,52 Kif23 kinesin family member 23 7 0.58 Kif22 kinesin family member 22 5 0.61 Nusap1 nucleolar and spindle associated protein 1 5 0.61 Cenpa centromere protein A 7 0.61 Cenpf centromere protein F 8 0.62 Kif11 kinesin family member 11 10 0.62 Cell communication Xlkd1 extra cellular link domain-containing 1 9 0.52 Efemp1 epidermal growth factor-containing fibulin-like extracellular 5 0.52 matrix protein 1 Differentiation Hoxc8 homeobox C8 3 0.57 Bmp4 bone morphogenetic protein 4 3 0.59 Iqgap3 Q motif containing GTPase activating protein 3 5 0.61 Metabolism Adipoq adiponectin 6 0.40 Cbr2 carbonyl reductase 2 4 0.48 Lpl lipoprotein lipase 6 0.58 Hnrpdl heterogeneous nuclear ribonucleoprotein D-like 10 0,61 Syncrip synaptotagmin binding, cytoplasmic RNA 4 0,61 Pdk1 pyruvate dehydrogenase kinase. isoenzyme 1 8 0.64 Acsl1 acyl-CoA synthetase long-chain family member 1 3 0.66 Immune system Ccl6 chemokine (C-C motif) ligand 6 12 0,47 Ccl8 chemokine (C-C motif) ligand 7 0,47 Cd5l CD5 antigen-like 7 0,50 Spib Spi-B transcription factor (Spi-1/PU.1 related) 3 0,56 Bcl6 B-cell leukemia/lymphoma 6 3 0,66 Stress response Alas2 aminolevulinic acid synthase 2 5 0.46 Cirbp cold inducible RNA binding protein 9 0.54 Lrmp lymphoid-restricted membrane protein 4 0.56 Zfp292 zinc finger protein 292 4 0.61 Sorbs3 sorbin and SH3 domain containing 3 3 0.53 Gpr133 -coupled receptor 133 3 0.62 Transcription Klf6 Kruppel-like factor 6 9 0.63 Mxd3 Max dimerization protein 3 6 0.66 Others Kctd14 potassium channel tetramerisation domain containing 14 3 0,50 Mrc1 mannose receptor, C type 1 3 0,53 Marco macrophage receptor with collagenous structure 3 0,56 Mgl1 macrophage galactose N-acetyl-galactosamine specific lectin 1 4 0,56 Folr2 folate receptor 2 (fetal) 3 0,57 Crym crystallin, mu 5 0,58 C79407 expressed sequence C79407 3 0.61 6720460F02Rik 4 0.62 March7 membrane-associated ring finger (C3HC4) 7 4 0,65 Shcbp1 Shc SH2-domain binding protein 1 4 0.65

5 Table S6: Genes up-regulated in P03 tumors at CT4 after meal timing.

Biological Process Symbol Gene name Coverage Fold change Cell cycle Nov nephroblastoma overexpressed gene 14 1.95 Pdrg1 p53 and DNA damage regulated 1 8 1.69 Ccnd2 cyclin D2 5 1.66 Cdkn1a cyclin-dependent kinase inhibitor 1A (P21) 7 1.63 Creld2 cysteine-rich with EGF-like domains 2 5 1.57 Ccng1 cyclin G1 15 1.56 Cell organization Col11a1 procollagen, type XI, alpha 1 5 1.97 Trim17 tripartite motif protein 17 3 1.64 Nefh neurofilament. heavy polypeptide 3 1.62 Tln1 talin 1 3 1.53 Differentiation Bhlhb8 basic helix-loop-helix domain containing, class B. 8 8 1.97 Gas6 growth arrest specific 6 3 1.78 Hoxa1 homeo box A1 3 1.75 Itm2a integral membrane protein 2A 3 1.75 Phlda2 pleckstrin homology-like domain. family A, member 2 3 1.71 Sox9 SRY-box containing gene 9 3 1.63 Hyou1 hypoxia up-regulated 1 3 1.54 Metabolism Prss12 protease Serine 12 neurotrypsin (motopsin) 4 1.76 Acad11 acyl-Coenzyme A dehydrogenase family, member 11 3 1.70 Padi3 peptidyl arginine deiminase, type III 5 1.60 Mest mesoderm specific transcript 5 1.61 Alox15 arachidonate 15-lipoxygenase 3 1.61 Fusip1 FUS interacting protein (serine-arginine rich) 1 3 1.61 Rbm4 RNA binding motif protein 4 3 1.60 Ncbp2 nuclear cap binding protein subunit 2 11 1.59 Alg2 sparagine-linked glycosylation 2 homolog 3 1.58 Rpl36a ribosomal protein L36a 3 1.53 Pgpep1 pyroglutamyl-peptidase I 5 1.52 Immune system Fkbp11 FK506 binding protein 11 6 1.56 Trim46 tripartite motif protein 46 3 1.55 H13 histocompatibility 13 3 1.54 Stress response Hspa1b heat shock protein 1B 9 2.99 Hsp110 heat shock protein 110 21 2.02 Hspa8 heat shock protein 8 10 1.92 Hspa4l heat shock protein 4 like 12 1.83 Dnajb10 DnaJ (Hsp40) homolog. subfamily B, member 10 9 1.73 Dnaja4 DnaJ (Hsp40) homolog. Subfamily A, member 4 10 1.63 Dnajb1 DnaJ (Hsp40) homolog. Subfamily B, member 1 14 1.60 Dnajb4 DnaJ (Hsp40) homolog. Subfamily B, member 4 4 1.60 Signal transduction Cabp1 calcium binding protein 1 9 3.08 Rasl11b RAS-like. family 11, member B 7 1.64 Shank3 SH3/ankyrin domain gene 3 5 1.63 Gpr172b G protein-coupled receptor 172B 3 1.61 Rasd2 RASD family, member 2 4 1.60 Dusp19 dual specificity phosphatase 19 6 1.57 Transcription Insm1 insulinoma-associated 1 8 1.99 Elavl2 ELAV (embryonic lethal. abnormal vision, Drosophila)-like 2 4 1.73 Preb prolactin regulatory element binding 6 1.58 Polr3k polymerase (RNA) III (DNA directed) polypeptide K 4 1.57 Others Wdr78 WD repeat domain 78 4 1.85 Chordc1 cysteine and histidine-rich domain (CHORD)-containing, 9 1.80 zinc-binding protein 1 D4Wsu53e DNA segment, Chr 4, Wayne State University 53, expressed 15 1.79 Sfi Sfi homolog 3 1.76 1110064P04Rik 9 1.73 D2Ertd435e DNA segment, Chr 2, ERATO Doi 435, expressed 3 1.68 Tex13 testis expressed gene 13 5 1.66 Abcc6 ATP-binding cassette, sub-family C (CFTR/MRP), member 6 3 1.60 3110048E14Rik 3 1.57 Ccdc117 coiled-coil domain containing 117 6 1.57 Reep6 receptor accessory protein 6 4 1.57 9030617O03Rik 5 1.56 Tmem126a transmembrane protein 126A 3 1.53

6 Table S6. Continued

Biological Process Symbol Gene name Coverage Fold change 1110057K04Rik 3 1.52 BC022687 3 1.52

7 Table S7: Genes down-regulated in P03 tumors at CT16 after meal timing.

Biological Process Symbol Gene name Coverage Fold change Cell cycle Cend1 cell cycle exit and neuronal differentiation 1 3 0.44 fAhr cell division cycle 6 homolog 5 0.65 Ccng1 cyclin G1 4 0.65 Nedd9 neural precursor cell expressed, developmentally 4 0.65 down-regulated gene 9 Cdk5 cyclin-dependent kinase 5 3 0.65 Cell communication Tloc1 translocation protein 1 6 0.58 Igfals insulin-like growth factor binding protein, acid labile subunit 5 0.64 Mpz myelin protein zero 4 0.65 Differentiation Insm1 insulinoma-associated 1 6 0.45 Trp53inp1 transformation related protein 53 inducible nuclear protein 1 6 0.55 Lgals12 lectin, galactose binding, soluble 12 3 0.61 Fzd2 frizzled homolog 2 9 0.63 Ift81 ntraflagellar transport 81 homolog 4 0.66 Metabolism Rbbp6 retinoblastoma binding protein 6 8 0.56 Tfrc transferrin receptor 5 0.59 Ncbp2 nuclear cap binding protein subunit 2 17 0.60 Pnliprp1 pancreatic lipase related protein 1 5 0.61 Sfrs7 splicing factor, arginine/serine-rich 7 4 0.61 Alas2 aminolevulinic acid synthase 2, erythroid 7 0.61 Scd2 stearoyl-Coenzyme A desaturase 2 15 0.62 Adpgk ADP-dependent glucokinase 6 0.62 Trib2 tribbles homolog 2 3 0.62 Slc30a2 solute carrier family 30 (zinc transporter), member 2 9 0.63 Slc25a15 solute carrier family 25 (mitochondrial carrier, 3 0.63 ornithine transporter), member 15 Alg12 asparagine-linked glycosylation 12 homolog 5 0.63 (yeast, alpha-1,6-mannosyltransferase) Sgpp1 sphingosine-1-phosphate phosphatase 1 9 0.63 Rbm4 RNA binding motif protein 4 5 0.63 Hmgcs2 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 5 0.63 Scrn3 secernin 3 6 0.63 Hsd17b11 hydroxysteroid (17-beta) dehydrogenase 11 3 0.64 Txndc5 thioredoxin domain containing 5 14 0.64 Fahd1 fumarylacetoacetate domain containing 1 4 0.64 Slc25a23 solute carrier family 25 (mitochondrial carrier; 3 0.64 phosphate carrier), member 23 Hs3st3b1 heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1 3 0.64 Sfrs1 splicing factor, arginine/serine-rich 1 (ASF/SF2) 13 0.64 Ube2h -conjugating E2H 5 0.65 Rpl22 ribosomal protein L22 4 0.65 Bxdc2 brix domain containing 2 7 0.66 Ubqln4 ubiquilin 4 5 0.66 Bpnt1 bisphosphate 3'-nucleotidase 1 7 0.66 Immune system Ltb lymphotoxin B 7 0.55 Cxcl4 chemokine (C-X-C motif) ligand 4 3 0.62 Fkbp4 FK506 binding protein 4 8 0.64 Nfkbia nuclear factor of kappa light chain gene 20 0.64 enhancer in B-cells inhibitor, alpha Tnfsf9 tumor necrosis factor (ligand) superfamily, member 9 4 0.65 Cd14 CD14 antigen 7 0.65 Relb avian reticuloendotheliosis viral (v-rel) oncogene related B 4 0.66 Stress response Hspa4l heat shock protein 4 like 6 0.49 Hspa8 heat shock protein 8 10 0.51 Hspa1b heat shock protein 1B 3 0.60 Dnajb10 DnaJ (Hsp40) homolog, subfamily B, member 10 6 0.60 Higd1a HIG1 domain family, member 1A 10 0.62 Dnajb9 DnaJ (Hsp40) homolog, subfamily B, member 9 5 0.63 Hsp110 heat shock protein 110 21 0.64 Serpinh1 serine (or cysteine) peptidase inhibitor, clade H, member 11 0.65 fTrp53inp1 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4 4 0.65 Ung uracil DNA glycosylase 4 0.65 Signal transduction Calm1 calmodulin 1 3 0.53 Nck1 non-catalytic region of tyrosine kinase adaptor protein 1 4 0.58

8 Table S7: Continued

Biological Process Symbol Gene name Coverage Fold change Foxc2 forkhead box C2 7 0.59 Tnfaip3 tumor necrosis factor, alpha-induced protein 3 4 0.60 Prkcbp1 C binding protein 1 6 0.62 Pkib protein kinase inhibitor beta, cAMP dependent, testis specific 3 0.62 H19 H19 fetal liver mRNA 5 0.62 Ptplad1 protein tyrosine phosphatase-like A domain containing 1 6 0.65 Prkaca protein kinase, cAMP dependent, catalytic, alpha 4 0.65 Transcription Gtf2i general transcription factor II I 6 0.59 Etv5 ets variant gene 5 4 0.59 Cebpa CCAAT/enhancer binding protein (C/EBP), alpha 3 0.60 Atf5 activating transcription factor 5 3 0.63 Banp Btg3 associated nuclear protein 5 0.63 Mafg v-maf musculoaponeurotic fibrosarcoma oncogene 4 0.64 family, protein G (avian) Sall2 sal-like 2 3 0.64 Zbtb12 zinc finger and BTB domain containing 12 5 0.64 Tsc22d1 TSC22 domain family, member 1 17 0.64 Sox9 SRY-box containing gene 9 13 0.65 Cebpg CCAAT/enhancer binding protein (C/EBP), gamma 7 0.65 Zkscan1 zinc finger with KRAB and SCAN domains 1 3 0.65 Cited4 Cbp/p300-interacting transactivator, with Glu/Asp-rich 4 0.66 carboxy-terminal domain, 4 Others Aplp2 amyloid beta (A4) precursor-like protein 2 3 0.48 D4Wsu53e DNA segment, Chr 4, Wayne State University 53, expressed 12 0.49 Oosp1 oocyte secreted protein 1 6 0.56 LOC673316 hypothetical protein LOC673316 3 0.58 2810441K11Rik 3 0.60 Cenpb centromere protein B 5 0.60 D3Ucla1 DNA segment, Chr 3, UCLA 1 9 0.62 Cd177 CD177 antigen 9 0.62 3300001P08Rik 6 0.62 6530401D17Rik 5 0.63 Pigh phosphatidylinositol glycan anchor biosynthesis, class H 3 0.63 Zfr zinc finger RNA binding protein 5 0.63 Cyhr1 cysteine and histidine rich 1 4 0.63 Tex13 testis expressed gene 13 5 0.63 D7Wsu128e DNA segment, Chr 7, Wayne State University 128, 3 0.63 expressed 1110003E01Rik 3 0.64 Mfap3 microfibrillar-associated protein 3 4 0.64 Igfbp4 insulin-like growth factor binding protein 4 18 0.64 C630004H02Rik 3 0.64 Tmcc2 transmembrane and coiled-coil domains 2 5 0.64 Klhdc5 kelch domain containing 5 8 0.64 1110054M08Rik 3 0.64 Chordc1 cysteine and histidine-rich domain (CHORD)-containing, 8 0.64 zinc-binding protein 1 A830007P12Rik 7 0.64 D11Ertd636e DNA segment, Chr 11, ERATO Doi 636, expressed 4 0.64 Gas5 growth arrest specific 5 14 0.65 1600014C10Rik 4 0.65 1810048J11Rik 8 0.65 Tmem14c transmembrane protein 14C 3 0.65 3110003A22Rik 5 0.65 1110064P04Rik 8 0.65 Leng1 leukocyte receptor cluster (LRC) member 1 3 0.65 2900062L11Rik 3 0.65 fEts1 RIKEN cDNA 1810049H13 gene 3 0.65 Tmem33 transmembrane protein 33 4 0.65 Gpatch8 G patch domain containing 8 5 0.66 2610020O08Rik 3 0.66 1110057K04Rik 8 0.66 Ccdc117 coiled-coil domain containing 117 6 0.66 Ngrn neugrin, neurite outgrowth associated 3 0.66 Nptx1 neuronal pentraxin 1 6 0.66 Sfi1 Sfi1 homolog, spindle assembly associated 3 0.66 Btbd14a BTB (POZ) domain containing 14A 5 0.66 Golph3 golgi phosphoprotein 3 7 0.66 Tulp3 tubby-like protein 3 4 0.66

9 Table S8: Genes up-regulated in P03 tumors at CT16 after meal timing.

Biological Process Symbol Gene name Coverage Fold change Cell cycle Nusap1 nucleolar and spindle associated protein 1 6 1,91 Ccnb1 cyclin B1 10 1,75 Tpd52l1 tumor protein D52-like 1 4 1,74 Cdca3 cell division cycle associated 3 7 1,69 Mki67 antigen identified by monoclonal antibody Ki 67 3 1,65 Sash1 SAM and SH3 domain containing 1 3 1,63 Aspm asp (abnormal spindle)-like, microcephaly associated 8 1,63 Cdc25b cell division cycle 25 homolog B (S. pombe) 4 1,62 Rbl1 retinoblastoma-like 1 (p107) 4 1,61 Cdc20 cell division cycle 20 homolog (S. cerevisiae) 8 1,59 Ccna2 cyclin A2 8 1,59 Plk1 polo-like kinase 1 (Drosophila) 5 1,57 Ect2 ect2 oncogene 5 1,57 Prc1 protein regulator of cytokinesis 1 15 1,56 Aurkb aurora kinase B 15 1,56 Ccnb2 cyclin B2 6 1,56 Csnk2a2 , alpha prime polypeptide 4 1,55 Incenp inner centromere protein 12 1,55 Topbp1 topoisomerase (DNA) II beta binding protein 3 1,53 Cep55 centrosomal protein 55 4 1,53 Pkmyt1 protein kinase, membrane associated tyrosine/threonine 1 4 1,53 Cdca4 cell division cycle associated 4 3 1,52 Cell proliferation Ndrg1 N-myc downstream regulated gene 1 15 1,58 Nov nephroblastoma overexpressed gene 3 1,56 Slfn4 schlafen 4 3 1,55 Evi2a ecotropic viral integration site 2a 3 1,52 Pdgfrb platelet derived growth factor receptor, beta polypeptide 6 1,52 Cell organization Cenpf centromere protein F 12 1,74 Cep110 centrosomal protein 110 3 1,70 Kif11 kinesin family member 11 14 1,64 Kif22 kinesin family member 22 21 1,64 Kif23 kinesin family member 23 8 1,64 Cenpa centromere protein A 8 1,63 Coro2a coronin, actin binding protein 2A 4 1.60 Mapre1 microtubule-associated protein, RP/EB family, member 1 6 1,59 Kif2c kinesin family member 2C 17 1,59 Sync syncoilin 3 1.58 Kif4 kinesin family member 4 9 1,58 Epb4.1I1 erythrocyte protein band 4.1-like 1 5 1.56 Tpx2 TPX2, microtubule-associated protein homolog 8 1,54 Cell Communication Mmp12 matrix metallopeptidase 12 5 1,77 fAtf5 matrix metallopeptidase 13 4 1.77 Spon1 spondin 1, (f-spondin) extracellular matrix protein 5 1,73 Tgfbi transforming growth factor, beta induced 30 1,66 Pcdh7 protocadherin 7 3 1,58 Differentiation Speg SPEG complex locus 6 1.91 Tnnt2 troponin T2, cardiac 3 1,78 Efnb2 ephrin B2 3 1,63 Cd300lf CD300 antigen like family member F 3 1,60 Egln3 EGL nine homolog 3 (C. elegans) 6 1.60 Cntfr ciliary neurotrophic factor receptor 3 1,58 Cdk5r1 cyclin-dependent kinase 5, regulatory subunit (p35) 1 4 1,58 Foxm1 forkhead box M1 5 1,58 P2rx1 purinergic receptor P2X, ligand-gated ion channel, 1 3 1,57 Iapp islet amyloid polypeptide 4 1,54 Gna13 guanine nucleotide binding protein, alpha 13 4 1,53 Bik Bcl2-interacting killer 3 1,59 Metabolism B4galt7 xylosylprotein beta1,4-galactosyltransferase, 3 2,48 polypeptide 7 (galactosyltransferase I) Adh7 alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide6 2,20 Zfy2 zinc finger protein 2, Y linked 3 2,11 Slc17a2 solute carrier family 17 (sodium phosphate), member 2 3 2,01 Steap3 STEAP family member 3 3 1,99 Ptpn5 protein tyrosine phosphatase, non-receptor type 5 4 1,97 Pga5 pepsinogen 5, group I 1,90 Plcb2 , beta 2 3 1,79

10 Opn4 opsin 4 (melanopsin) 3 1,78 Pcolce procollagen C-endopeptidase enhancer protein 4 1,77 Ela3 elastase 3, pancreatic 3 1,76 Slc44a1 solute carrier family 44, member 1 3 1,75 Ubc ubiquitin C 4 1.75 Enpp1 ectonucleotide pyrophosphatase/phosphodiesterase 1 3 1.71 Slc1a4 Solute carrier family 1 (glutamate/neutral amino acid 8 1,71 transporter), member 4 Rnf141 ring finger protein 141 3 1,52 Slc14a1 solute carrier family 14 (urea transporter), member 1 5 1,70 Slc2a1 solute carrier family 2 (facilitated glucose transporter), 6 1,69 member 1 Slc5a2 solute carrier family 5 (sodium/glucose cotransporter), 4 1,68 member 2 C1galt1c1 C1GALT1-specific chaperone 1 3 1,66 Pcbp2 poly(rC) binding protein 2 9 1.65 H1f0o H1 histone family, member O, oocyte-specific 3 1,54 C1qtnf3 C1q and tumor necrosis factor related protein 3 3 1,64 Mtch2 mitochondrial carrier homolog 2 10 1,63 Dqx1 DEAQ RNA-dependent ATPase 3 1,63 Utf1 undifferentiated embryonic cell transcription factor 1 3 1,63 Lct lactase 3 1,61 Wdr33 WD repeat domain 33 4 1,61 Arrdc4 arrestin domain containing 4 3 1,60 Syncrip synaptotagmin binding, cytoplasmic RNA interacting protein 6 1,60 Laptm5 lysosomal-associated protein transmembrane 5 4 1,60 Col20a1 collagen, type XX, alpha 1 3 1,58 Msr1 macrophage scavenger receptor 1 3 1,58 Fech ferrochelatase 4 1,57 Tcerg1 transcription elongation regulator 1 (CA150) 3 1,57 Hnrpk heterogeneous nuclear ribonucleoprotein K 3 1,57 Hnrpab heterogeneous nuclear ribonucleoprotein A/B 3 1,57 Melk maternal embryonic leucine zipper kinase 9 1,57 Sf1 splicing factor 1 4 1,57 Art5 ADP-ribosyltransferase 5 4 1,57 Atcay ataxia, cerebellar, Cayman type homolog (human) 3 1,57 Hist1h1c histone cluster 1, H1c 11 1,56 Ssb Sjogren syndrome antigen B 3 1,56 Ppargc1a peroxisome proliferative activated receptor, gamma, 7 1,56 coactivator 1 alpha Hnrpdl heterogeneous nuclear ribonucleoprotein D-like 0,637 1,56 Tgm2 transglutaminase 2, C polypeptide 0,63 1,55 Arih2 ariadne homolog 2 (Drosophila) 0,63 1,55 Elac2 elaC homolog 2 (E. coli) 0,628 1,55 H1f0 H1 histone family, member 0 0,627 1,54 Lass4 longevity assurance homolog 4 (S. cerevisiae) 0,621 1,54 Auh AU RNA binding protein/enoyl-coenzyme A hydratase 0,62 1,54 Tiparp TCDD-inducible poly(ADP-ribose) polymerase 0,616 1,53 Raly hnRNP-associated with lethal yellow 0,612 1,53 Scara3 scavenger receptor class A, member 3 0,607 1,52 Syt2 synaptotagmin II 0,605 1,52 Pdia4 protein disulfide associated 4 0,603 1,52 Ugt3a2 UDP glycosyltransferases 3 family, polypeptide A2 0,601 1,52 Immune system Csf1 colony stimulating factor 1 (macrophage) 4 2,10 Clec7a C-type lectin domain family 7, member a 6 1,84 Cd8b1 CD8 antigen, beta chain 1 3 1,77 Irf7 interferon regulatory factor 7 3 1,71 Gbp3 guanylate nucleotide binding protein 3 7 1,70 Isg15 ISG15 ubiquitin-like modifier 14 1,67 Oasl2 2'-5' oligoadenylate synthetase-like 2 8 1,66 Il16 interleukin 16 4 1,65 Ccr9 chemokine (C-C motif) receptor 9 3 1,66 H2-Aa histocompatibility 2, class II antigen A, alpha 5 1,65 H2-Q10 histocompatibility 2, Q region locus 10 4 1,64 Nkx2-3 K2 transcription factor related 3 1,63 Tap1 transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)5 1,62 Mmp9 matrix metallopeptidase 9 3 1,61 Ccr2 chemokine (C-C motif) receptor 2 4 1,58 Cxcl16 chemokine (C-X-C motif) ligand 16 3 1,57 Ccl17 chemokine (C-C motif) ligand 17 3 1,54 Ifit1 interferon-induced protein with tetratricopeptide repeats 1 3 1,54 Traf6 Tnf receptor-associated factor 6 4 1,53 Ets1 E26 avian leukemia oncogene 1, 5' domain 5 1,53 Itgb2 integrin beta 2 4 1,52

11 Table S8: Continued

Biological Process Symbol Gene name Coverage Fold change Mx1 myxovirus (influenza virus) resistance 1 4 1,52 Stress response Serpinc1 serine (or cysteine) peptidase inhibitor, clade C 3 1,95 (antithrombin), member 1 Prdx1 peroxiredoxin 1 9 1,87 Cirbp cold inducible RNA binding protein 7 1,76 Serping1 serine (or cysteine) peptidase inhibitor, clade G, member 1 5 1,56 Gna13 colony stimulating factor 1 receptor 5 1,54 Signal transduction Gngt1 guanine nucleotide binding protein (G protein), gamma 7 1,98 transducing activity polypeptide 1 Itga5 integrin alpha 5 (fibronectin receptor alpha) 3 1,88 Mical1 microtubule associated monoxygenase, calponin and 3 1,74 LIM domain containing 1 Grik3 glutamate receptor, ionotropic, kainate 3 3 1,73 Fmod fibromodulin 4 1,72 Hip1 huntingtin interacting protein 1 6 1,72 D0H4S114 DNA segment, human D4S114 9 1,71 Iigp1 interferon inducible GTPase 1 11 1,68 Depdc1a DEP domain containing 1a 3 1,67 Pde6h phosphodiesterase 6H, cGMP-specific, cone, gamma 3 1,67 Lypd1 Ly6/Plaur domain containing 1 3 1,66 Trp63 transformation related protein 63 3 1,66 Camkv CaM kinase-like vesicle-associated 3 1,65 Tnc tenascin C 7 1,64 Fgl2 fibrinogen-like protein 2 3 1,62 Stmn3 stathmin-like 3 4 1,60 Csf2rb1 colony stimulating factor 2 receptor, beta 1, 3 1,59 low-affinity (granulocyte-macrophage) Mark2 MAP/microtubule affinity-regulating kinase 2 3 1,59 Gabra1 gamma-aminobutyric acid (GABA-A) receptor, 3 1,58 subunit alpha 1 Mrpl13 mitochondrial ribosomal protein L13 3 1,57 Igfbp5 insulin-like growth factor binding protein 5 4 1,57 Rad21 RAD21 homolog (S. pombe) 13 1,56 Epha3 Eph receptor A3 4 1,56 Drd4 dopamine receptor 4 3 1,55 Cabyr calcium-binding tyrosine-(Y)-phosphorylation regulated 4 1,55 (fibrousheathin 2) Akap4 A kinase (PRKA) anchor protein 4 4 1,55 Insl6 insulin-like 6 4 1,55 Ms4a4b membrane-spanning 4-domains, subfamily A, member 4B 4 1,54 Rims2 regulating synaptic membrane exocytosis 2 5 1,54 Magi1 membrane associated guanylate kinase, WW and 4 1,54 PDZ domain containing 1 Arhgap21 Rho GTPase activating protein 21 4 1,53 Ttk Ttk protein kinase 4 1,53

Transcription Bclaf1 BCL2-associated transcription factor 1 6 1,72 Esr2 estrogen receptor 2 (beta) 3 1,66 Mef2c myocyte enhancer factor 2C 4 1,60 Akna AT-hook transcription factor 3 1,59 Zbtb44 zinc finger and BTB domain containing 44 4 1,58 Med12 mediator of RNA polymerase II transcription, 3 1,55 subunit 12 homolog (yeast) Klf6 Kruppel-like factor 6 8 1,54 Prrx1 paired related homeobox 1 4 1,54 Ahr aryl-hydrocarbon receptor 4 1,54 Rora RAR-related orphan receptor alpha 3 1,54 Tcfap2a transcription factor AP-2, alpha 15 1,52 Rnf141 ring finger protein 141 3 1,52 Others Odf3 outer dense fiber of sperm tails 3 3 1,87 Pramel7 preferentially expressed antigen in melanoma like 7 3 1,85 BC026682 cDNA sequence BC026682 3 1,84 Rtp4 receptor transporter protein 4 4 1,73 C79407 expressed sequence C79407 9 1,71 Rbmx RNA binding motif protein, X 6 1,67 Trdn triadin 6 1,66 Shcbp1 Shc SH2-domain binding protein 1 9 1,64

12 Table S8: Continued

Biological Process Symbol Gene name Coverage Fold change U46068 cDNA sequence U46068 3 1,64 Crispld1 cysteine-rich secretory protein LCCL domain containing 1 3 1,64 Trav7d-6 T-cell receptor alpha variable region 7D-6 4 1,63 Apcdd1 adenomatosis polyposis coli down-regulated 1 4 1,62 Marcks myristoylated alanine rich substrate 9 1,62 Impg1 interphotoreceptor matrix proteoglycan 1 3 1,62 Gnl2 guanine nucleotide binding protein-like 2 (nucleolar) 5 1,60 Serpini1 serine (or cysteine) peptidase inhibitor, clade I, member 1 3 1,59 Mpeg1 macrophage expressed gene 1 6 1,59 Hmmr hyaluronan mediated motility receptor (RHAMM) 5 1,58 1810010M01Rik 3 1,58 1700037H04Rik 3 1,58 Nsmce4a non-SMC element 4 homolog A (S. cerevisiae) 3 1,58 Prdx4 peroxiredoxin 4 3 1,57 2810485I05Rik 3 1,56 Sharpin SHANK-associated RH domain interacting protein 3 1,56 Cd52 CD52 antigen 3 1,56 Zbp1 Z-DNA binding protein 1 7 1,54 sad2 radical S-adenosyl methionine domain containing 2 17 1,54 Smtn smoothelin 3 1,53 E130108L08Rik 7 1,53 Ncapg on-SMC condensin I complex, subunit G 1,52 Nucks1 nuclear casein kinase and cyclin-dependent kinase 4 1,52 substrate 1 Reps1 RalBP1 associated Eps domain containing protein 3 1,52

13