Supplemental Table S7: GO pathway analysis for proximal to differential enriched binding sites

GO pathways for ER-associated genes

GO term Description P-value FDR q-value Enrichment (N, B, n, b) Genes GO:0019427 acetyl-CoA biosynthetic process from acetate 7.17E-05 8.31E-01 117.68 (17416,2,148,2) ACSS1 - acyl-coa synthetase short-chain family member 1 ACSS2 - acyl-coa synthetase short-chain family member 2

GO:0008154 actin polymerization or depolymerization 1.69E-04 9.79E-01 14.26 (17416,33,148,4) EVL - enah/vasp-like WIPF1 - was/wasl interacting family, member 1 GSN - gelsolin MICAL2 - microtubule associated monoxygenase, calponin and lim domain containing 2

GO:0006083 acetate metabolic process 2.14E-04 8.26E-01 78.45 (17416,3,148,2) ACSS1 - acyl-coa synthetase short-chain family member 1 ACSS2 - acyl-coa synthetase short-chain family member 2

GO:0071316 cellular response to nicotine 4.26E-04 1.00E+00 58.84 (17416,4,148,2) BAD - bcl2-associated agonist of cell death TH - tyrosine hydroxylase

GO:0017158 regulation of calcium ion-dependent exocytosis 8.23E-04 1.00E+00 16.05 (17416,22,148,3) B4GALT1 - udp-gal:betaglcnac beta 1,4- galactosyltransferase, polypeptide 1 CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit RPH3AL - rabphilin 3a-like (without c2 domains)

GO pathways for H3K4me3-associated genes

GO term Description P-value FDR q-value Enrichment (N, B, n, b) Genes GO:0015858 nucleoside transport 2.27E-04 1.00E+00 87.96 (17416,12,33,2) SLC28A3 - solute carrier family 28 (sodium-coupled nucleoside transporter), member 3 GJA1 - gap junction protein, alpha 1, 43kda

GO:0050921 positive regulation of chemotaxis 4.12E-04 1.00E+00 20.56 (17416,77,33,3) VEGFB - vascular endothelial growth factor b GAS6 - growth arrest-specific 6 DSCAM - down syndrome cell adhesion molecule

GO:0048520 positive regulation of behavior 6.09E-04 1.00E+00 17.99 (17416,88,33,3) VEGFB - vascular endothelial growth factor b GAS6 - growth arrest-specific 6 DSCAM - down syndrome cell adhesion molecule

GO:0045766 positive regulation of angiogenesis 6.51E-04 1.00E+00 17.59 (17416,90,33,3) GATA2 - gata binding protein 2 VEGFB - vascular endothelial growth factor b CX3CR1 - chemokine (c-x3-c motif) receptor 1

GO:0032879 regulation of localization 8.64E-04 1.00E+00 3.41 (17416,1393,33,9) VEGFB - vascular endothelial growth factor b GATA2 - gata binding protein 2 RABGAP1L - rab gtpase activating protein 1-like GAS6 - growth arrest-specific 6 DSCAM - down syndrome cell adhesion molecule CX3CR1 - chemokine (c-x3-c motif) receptor 1 CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit ALOX15B - arachidonate 15-lipoxygenase, type b GJA1 - gap junction protein, alpha 1, 43kda

GO:0050920 regulation of chemotaxis 9.91E-04 1.00E+00 15.22 (17416,104,33,3) VEGFB - vascular endothelial growth factor b GAS6 - growth arrest-specific 6 DSCAM - down syndrome cell adhesion molecule

GO pathways for H3K27me3-associated genes

GO term Description P-value FDR q-value Enrichment (N, B, n, b) Genes GO:0060762 regulation of branching involved in mammary gland duct morphogenesis1.24E-05 1.45E-01 57.85 (17703,6,153,3) ETV4 - ets variant 4 WNT5A - wingless-type mmtv integration site family, member 5a TGFB1 - transforming growth factor, beta 1

GO:0048856 anatomical structure development 2.58E-05 1.50E-01 1.95 (17703,2320,153,39) IRS1 - substrate 1 TP53BP2 - tumor protein p53 binding protein, 2 WNT11 - wingless-type mmtv integration site family, member 11 CRIM1 - cysteine rich transmembrane bmp regulator 1 (chordin-like) TNFRSF11B - tumor necrosis factor receptor superfamily, member 11b GLI2 - gli family zinc finger 2 GNG8 - guanine nucleotide binding protein (g protein), gamma 8 CHRNA3 - cholinergic receptor, nicotinic, alpha 3 (neuronal) FGF3 - fibroblast growth factor 3 NTRK3 - neurotrophic tyrosine kinase, receptor, type 3 CA2 - carbonic anhydrase ii NAV2 - neuron navigator 2 KRTAP5-9 - keratin associated protein 5-9 SEMA5B - sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (tm) and short cytoplasmic domain, (semaphorin) 5b WNT5A - wingless-type mmtv integration site family, member 5a TSKU - tsukushi small leucine rich proteoglycan homolog (xenopus laevis) CA10 - carbonic anhydrase x FOXN3 - forkhead box n3 LMO2 - lim domain only 2 (rhombotin-like 1) MEIS1 - meis homeobox 1 FAM65B - family with sequence similarity 65, member b GNAS - gnas complex locus TGFB1 - transforming growth factor, beta 1 HOMER1 - homer homolog 1 (drosophila) TG - thyroglobulin NPAS2 - neuronal pas domain protein 2 IGF1R - insulin-like growth factor 1 receptor FGF19 - fibroblast growth factor 19 ACTA2 - actin, alpha 2, smooth muscle, aorta OCA2 - oculocutaneous albinism ii FAM20C - family with sequence similarity 20, member c MAF - v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian) LIF - leukemia inhibitory factor CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit GAL - galanin prepropeptide THBD - thrombomodulin FAS - fas (tnf receptor superfamily, member 6) PODXL - podocalyxin-like COL11A2 - collagen, type xi, alpha 2

GO:0009719 response to endogenous stimulus 2.88E-05 1.12E-01 2.57 (17703,1037,153,23) IRS1 - insulin receptor substrate 1 LMO2 - lim domain only 2 (rhombotin-like 1) SLIT3 - slit homolog 3 (drosophila) GNAS - gnas complex locus CHRNA5 - cholinergic receptor, nicotinic, alpha 5 (neuronal) TNFRSF11B - tumor necrosis factor receptor superfamily, member 11b AQP9 - aquaporin 9 GRIN2A - glutamate receptor, ionotropic, n-methyl d-aspartate 2a GNG8 - guanine nucleotide binding protein (g protein), gamma 8 TGFB1 - transforming growth factor, beta 1 HOMER1 - homer homolog 1 (drosophila) CHRNA3 - cholinergic receptor, nicotinic, alpha 3 (neuronal) FGF3 - fibroblast growth factor 3 FGF4 - fibroblast growth factor 4 IGF1R - insulin-like growth factor 1 receptor NTRK3 - neurotrophic tyrosine kinase, receptor, type 3 FGF19 - fibroblast growth factor 19 CA2 - carbonic anhydrase ii FNTA - farnesyltransferase, caax box, alpha WNT5A - wingless-type mmtv integration site family, member 5a CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit GAL - galanin prepropeptide FAS - fas (tnf receptor superfamily, member 6)

GO:0032502 developmental process 3.86E-05 1.13E-01 1.65 (17703,3849,153,55) PTPRM - protein tyrosine phosphatase, receptor type, m WNT11 - wingless-type mmtv integration site family, member 11 TNFRSF11B - tumor necrosis factor receptor superfamily, member 11b CHRNA3 - cholinergic receptor, nicotinic, alpha 3 (neuronal) NAV2 - neuron navigator 2 WNT5A - wingless-type mmtv integration site family, member 5a SEMA5B - sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (tm) and short cytoplasmic domain, (semaphorin) 5b FOXN3 - forkhead box n3 LMO2 - lim domain only 2 (rhombotin-like 1) PLCG2 - phospholipase c, gamma 2 (phosphatidylinositol-specific) ETV4 - ets variant 4 FAM65B - family with sequence similarity 65, member b ANTXR1 - anthrax toxin receptor 1 RING1 - ring finger protein 1 LGI4 - leucine-rich repeat lgi family, member 4 ACTA2 - actin, alpha 2, smooth muscle, aorta OCA2 - oculocutaneous albinism ii FAM20C - family with sequence similarity 20, member c LIF - leukemia inhibitory factor GAL - galanin prepropeptide FAS - fas (tnf receptor superfamily, member 6) IRS1 - insulin receptor substrate 1 TP53BP2 - tumor protein p53 binding protein, 2 CRIM1 - cysteine rich transmembrane bmp regulator 1 (chordin-like) GLI2 - gli family zinc finger 2 GNG8 - guanine nucleotide binding protein (g protein), gamma 8 FGF3 - fibroblast growth factor 3 FGF4 - fibroblast growth factor 4 CA2 - carbonic anhydrase ii NTRK3 - neurotrophic tyrosine kinase, receptor, type 3 KRTAP5-9 - keratin associated protein 5-9 NEO1 - neogenin 1 BTG4 - b-cell translocation 4 TSKU - tsukushi small leucine rich proteoglycan homolog (xenopus laevis) CA10 - carbonic anhydrase x IGF2BP2 - insulin-like growth factor 2 mrna binding protein 2 MEIS1 - meis homeobox 1 SLIT3 - slit homolog 3 (drosophila) GNAS - gnas complex locus GRIN2A - glutamate receptor, ionotropic, n-methyl d-aspartate 2a TGFB1 - transforming growth factor, beta 1 HOMER1 - homer homolog 1 (drosophila) PRTG - protogenin KIF26B - kinesin family member 26b TG - thyroglobulin SLFN5 - schlafen family member 5 IGF1R - insulin-like growth factor 1 receptor NPAS2 - neuronal pas domain protein 2 FGF19 - fibroblast growth factor 19 MAF - v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian) CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit THBD - thrombomodulin PAPPA2 - pappalysin 2 PODXL - podocalyxin-like COL11A2 - collagen, type xi, alpha 2

GO:0022407 regulation of cell-cell adhesion 4.31E-05 1.00E-01 9.38 (17703,74,153,6) FXYD5 - fxyd domain containing ion transport regulator 5 WNT5A - wingless-type mmtv integration site family, member 5a TGFB1 - transforming growth factor, beta 1 KIF26B - kinesin family member 26b MYO10 - myosin x PODXL - podocalyxin-like

GO:0061035 regulation of cartilage development 5.17E-05 1.00E-01 12.31 (17703,47,153,5) WNT11 - wingless-type mmtv integration site family, member 11 MAF - v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian) GLI2 - gli family zinc finger 2 WNT5A - wingless-type mmtv integration site family, member 5a TGFB1 - transforming growth factor, beta 1

GO:0009725 response to hormone stimulus 1.23E-04 2.04E-01 2.92 (17703,634,153,16) IRS1 - insulin receptor substrate 1 LMO2 - lim domain only 2 (rhombotin-like 1) SLIT3 - slit homolog 3 (drosophila) GNAS - gnas complex locus TNFRSF11B - tumor necrosis factor receptor superfamily, member 11b GNG8 - guanine nucleotide binding protein (g protein), gamma 8 TGFB1 - transforming growth factor, beta 1 FGF3 - fibroblast growth factor 3 IGF1R - insulin-like growth factor 1 receptor FGF4 - fibroblast growth factor 4 CA2 - carbonic anhydrase ii FGF19 - fibroblast growth factor 19 NTRK3 - neurotrophic tyrosine kinase, receptor, type 3 CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit GAL - galanin prepropeptide FAS - fas (tnf receptor superfamily, member 6)

GO:0014070 response to organic cyclic compound 1.49E-04 2.16E-01 3.16 (17703,513,153,14) SLIT3 - slit homolog 3 (drosophila) GNAS - gnas complex locus CHRNA5 - cholinergic receptor, nicotinic, alpha 5 (neuronal) AQP9 - aquaporin 9 TNFRSF11B - tumor necrosis factor receptor superfamily, member 11b GLI2 - gli family zinc finger 2 TGFB1 - transforming growth factor, beta 1 HOMER1 - homer homolog 1 (drosophila) CHRNA3 - cholinergic receptor, nicotinic, alpha 3 (neuronal) IGF1R - insulin-like growth factor 1 receptor CA2 - carbonic anhydrase ii NTRK3 - neurotrophic tyrosine kinase, receptor, type 3 GAL - galanin prepropeptide FAS - fas (tnf receptor superfamily, member 6)

GO:0022409 positive regulation of cell-cell adhesion 1.60E-04 2.07E-01 14.46 (17703,32,153,4) WNT5A - wingless-type mmtv integration site family, member 5a KIF26B - kinesin family member 26b MYO10 - myosin x PODXL - podocalyxin-like

GO:2000647 negative regulation of stem cell proliferation 2.15E-04 2.50E-01 24.79 (17703,14,153,3) WNT11 - wingless-type mmtv integration site family, member 11 WNT5A - wingless-type mmtv integration site family, member 5a TGFB1 - transforming growth factor, beta 1

GO:0048009 insulin-like growth factor receptor signaling pathway 2.15E-04 2.28E-01 24.79 (17703,14,153,3) IRS1 - insulin receptor substrate 1 CRIM1 - cysteine rich transmembrane bmp regulator 1 (chordin-like) IGF1R - insulin-like growth factor 1 receptor

GO:0044767 single-organism developmental process 2.44E-04 2.37E-01 1.76 (17703,2571,153,39) IRS1 - insulin receptor substrate 1 PTPRM - protein tyrosine phosphatase, receptor type, m TP53BP2 - tumor protein p53 binding protein, 2 WNT11 - wingless-type mmtv integration site family, member 11 GLI2 - gli family zinc finger 2 FGF3 - fibroblast growth factor 3 FGF4 - fibroblast growth factor 4 NTRK3 - neurotrophic tyrosine kinase, receptor, type 3 CA2 - carbonic anhydrase ii NAV2 - neuron navigator 2 NEO1 - neogenin 1 WNT5A - wingless-type mmtv integration site family, member 5a TSKU - tsukushi small leucine rich proteoglycan homolog (xenopus laevis) CA10 - carbonic anhydrase x FOXN3 - forkhead box n3 LMO2 - lim domain only 2 (rhombotin-like 1) MEIS1 - meis homeobox 1 SLIT3 - slit homolog 3 (drosophila) ETV4 - ets variant 4 FAM65B - family with sequence similarity 65, member b GNAS - gnas complex locus ANTXR1 - anthrax toxin receptor 1 RING1 - ring finger protein 1 TGFB1 - transforming growth factor, beta 1 HOMER1 - homer homolog 1 (drosophila) KIF26B - kinesin family member 26b TG - thyroglobulin IGF1R - insulin-like growth factor 1 receptor FGF19 - fibroblast growth factor 19 LGI4 - leucine-rich repeat lgi family, member 4 ACTA2 - actin, alpha 2, smooth muscle, aorta OCA2 - oculocutaneous albinism ii FAM20C - family with sequence similarity 20, member c MAF - v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian) LIF - leukemia inhibitory factor CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit THBD - thrombomodulin FAS - fas (tnf receptor superfamily, member 6) PODXL - podocalyxin-like

GO:0032870 cellular response to hormone stimulus 2.94E-04 2.63E-01 3.55 (17703,359,153,11) IRS1 - insulin receptor substrate 1 FGF19 - fibroblast growth factor 19 LMO2 - lim domain only 2 (rhombotin-like 1) SLIT3 - slit homolog 3 (drosophila) GNAS - gnas complex locus GNG8 - guanine nucleotide binding protein (g protein), gamma 8 TGFB1 - transforming growth factor, beta 1 CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit FGF3 - fibroblast growth factor 3 IGF1R - insulin-like growth factor 1 receptor FGF4 - fibroblast growth factor 4

GO:0002682 regulation of immune system process 4.30E-04 3.58E-01 2.30 (17703,1007,153,20) IRS1 - insulin receptor substrate 1 LMO2 - lim domain only 2 (rhombotin-like 1) PACS1 - phosphofurin acidic cluster sorting protein 1 MEIS1 - meis homeobox 1 PLCG2 - phospholipase c, gamma 2 (phosphatidylinositol-specific) GNAS - gnas complex locus PRNP - prion protein GLI2 - gli family zinc finger 2 TGFB1 - transforming growth factor, beta 1 FGF3 - fibroblast growth factor 3 MYO10 - myosin x ZBP1 - z-dna binding protein 1 FGF4 - fibroblast growth factor 4 FGF19 - fibroblast growth factor 19 CA2 - carbonic anhydrase ii LIF - leukemia inhibitory factor WNT5A - wingless-type mmtv integration site family, member 5a LRRC32 - leucine rich repeat containing 32 GAL - galanin prepropeptide FAS - fas (tnf receptor superfamily, member 6)

GO:0007442 hindgut morphogenesis 4.40E-04 3.42E-01 57.85 (17703,4,153,2) GLI2 - gli family zinc finger 2 WNT5A - wingless-type mmtv integration site family, member 5a

GO:0048731 system development 4.95E-04 3.60E-01 2.68 (17703,647,153,15) WNT11 - wingless-type mmtv integration site family, member 11 TP53BP2 - tumor protein p53 binding protein, 2 CRIM1 - cysteine rich transmembrane bmp regulator 1 (chordin-like) TNFRSF11B - tumor necrosis factor receptor superfamily, member 11b GLI2 - gli family zinc finger 2 GNG8 - guanine nucleotide binding protein (g protein), gamma 8 CHRNA3 - cholinergic receptor, nicotinic, alpha 3 (neuronal) NPAS2 - neuronal pas domain protein 2 FGF19 - fibroblast growth factor 19 FAM20C - family with sequence similarity 20, member c LIF - leukemia inhibitory factor WNT5A - wingless-type mmtv integration site family, member 5a SEMA5B - sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (tm) and short cytoplasmic domain, (semaphorin) 5b GAL - galanin prepropeptide COL11A2 - collagen, type xi, alpha 2

GO:0010038 response to metal ion 6.24E-04 4.28E-01 4.25 (17703,218,153,8) CA2 - carbonic anhydrase ii AQP9 - aquaporin 9 TNFRSF11B - tumor necrosis factor receptor superfamily, member 11b PRNP - prion protein WNT5A - wingless-type mmtv integration site family, member 5a CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit HOMER1 - homer homolog 1 (drosophila) FAS - fas (tnf receptor superfamily, member 6)

GO:0050866 negative regulation of cell activation 6.42E-04 4.15E-01 5.74 (17703,121,153,6) PRNP - prion protein TGFB1 - transforming growth factor, beta 1 LRRC32 - leucine rich repeat containing 32 THBD - thrombomodulin GAL - galanin prepropeptide FAS - fas (tnf receptor superfamily, member 6)

GO:0072201 negative regulation of mesenchymal cell proliferation 7.30E-04 4.47E-01 46.28 (17703,5,153,2) WNT11 - wingless-type mmtv integration site family, member 11 WNT5A - wingless-type mmtv integration site family, member 5a

GO:0060744 mammary gland branching involved in thelarche 7.30E-04 4.25E-01 46.28 (17703,5,153,2) WNT5A - wingless-type mmtv integration site family, member 5a TGFB1 - transforming growth factor, beta 1

GO:0008285 negative regulation of cell proliferation 7.30E-04 4.05E-01 2.83 (17703,532,153,13) PTPRM - protein tyrosine phosphatase, receptor type, m WNT11 - wingless-type mmtv integration site family, member 11 PTGIR - prostaglandin i2 (prostacyclin) receptor (ip) SLIT3 - slit homolog 3 (drosophila) ETV4 - ets variant 4 PRNP - prion protein TGFB1 - transforming growth factor, beta 1 LIF - leukemia inhibitory factor VIPR2 - vasoactive intestinal peptide receptor 2 WNT5A - wingless-type mmtv integration site family, member 5a BTG4 - b-cell translocation gene 4 GAL - galanin prepropeptide LRRC32 - leucine rich repeat containing 32

GO:0030879 mammary gland development 7.51E-04 3.98E-01 16.53 (17703,21,153,3) IRS1 - insulin receptor substrate 1 GLI2 - gli family zinc finger 2 IGF1R - insulin-like growth factor 1 receptor

GO:0060444 branching involved in mammary gland duct morphogenesis 8.64E-04 4.38E-01 15.78 (17703,22,153,3) ETV4 - ets variant 4 WNT5A - wingless-type mmtv integration site family, member 5a TGFB1 - transforming growth factor, beta 1

GO:0040011 locomotion 9.66E-04 4.69E-01 2.21 (17703,995,153,19) PLD1 - phospholipase d1, phosphatidylcholine-specific PTPRM - protein tyrosine phosphatase, receptor type, m SLIT3 - slit homolog 3 (drosophila) TUBB2B - tubulin, beta 2b class iib ETV4 - ets variant 4 PRNP - prion protein GLI2 - gli family zinc finger 2 GRIN2A - glutamate receptor, ionotropic, n-methyl d-aspartate 2a TGFB1 - transforming growth factor, beta 1 MYO10 - myosin x CCL20 - chemokine (c-c motif) ligand 20 NTRK3 - neurotrophic tyrosine kinase, receptor, type 3 FGF19 - fibroblast growth factor 19 NEO1 - neogenin 1 WNT5A - wingless-type mmtv integration site family, member 5a CACNA1H - calcium channel, voltage-dependent, t type, alpha 1h subunit THBD - thrombomodulin PAK7 - p21 protein (cdc42/rac)-activated kinase 7 PODXL - podocalyxin-like

N - is the total number of genes B - is the total number of genes associated with a specific GO term n - is the number of genes in the top of the user's input list or in the target set when appropriate b - is the number of genes in the intersection Enrichment = (b/n) / (B/N)