EGAGenomicsIllumina Bisulfite-Sequencinghttps://ega-archive.org/datasets/EGAD0001000086816EGA dataset EGAD00010000868EGAThe transforming growth factor beta (TGF-β) signaling pathway exerts opposing effects on cancer cells, acting as either a tumor promoter or a tumor suppressor. Here, we show that these opposing effects are a result of the synergy between SMAD3, a downstream effector of TGF-β signaling, and the distinct epigenomes of breast-tumor-initiating cells (BTICs). These effects of TGF-β are associated with distinct gene expression programs, but genomic SMAD3 binding patterns are highly similar in the BTIC-promoting and BTIC-suppressing contexts. Our data show cell-type-specific patterns of DNA and histone modifications provide a modulatory layer by determining accessibility of genes to regulation by TGF-β/SMAD3. LBH, one such context-specific target gene, is regulated according to its DNA methylation status and is crucial for TGF-β-dependent promotion of BTICs. Overall, these results reveal that the epigenome plays a central and previously overlooked role in shaping the context-specific effects of TGF-β in cancer.Context-Specific Effects of TGF-β/SMAD3 in Cancer Are Modulated by the Epigenome.Tufegdzic Vidakovic Ana A, Rueda Oscar M OM, Vervoort Stephin J SJ, Sati Batra Ankita A, Goldgraben Mae Akilina MA, Uribe-Lewis Santiago S, Greenwood Wendy W, Coffer Paul J PJ, Bruna Alejandra A, Caldas Carlos CAZATHIOPRINE, AZA, 6-[(1-Methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine, AZTP, Azathioprine.DNA Methylome., LDS1C, SMAD family member 3, Malignant Neoplasm, JV15-2, Methylomes, Neoplasms, Madh3, Benign Neoplasm, Tumor, LDS3, Malignant, XenMLP, Mad3, MT, Benign, HsT17436, SMAD 3, Xmad3, Neoplasm, madh3-A, XSmad3, Methylome, hMAD-3, Smad 3, MADH3, hSMAD3, primary cancer, Malignancy, Epigenomes, mad3, mMad3, Benign Neoplasms, Cancers, DNA Methylomes, malignant tumor, Malignant Neoplasms, Neoplasias, HSPC193, MAD homolog 3, AU022421, malignant neoplasm, Mothers against DPP homolog 3, Smad3, Malignancies, DNA, Neoplasia, Cancer, TumorsH2S(D2S), hydrosulfite., bisulfiteMGC130048, SMAD family member 3, Breasts, target gene, Materials, transforming growth factor beta ligand binding to type I receptor, tumor suppressor, Lactiferous gland, A4, DNA Methylations, Tumor, XenMLP, glandula mammaria, Social Controls, Milk, TGFbeta, Milk Growth Factor, dmTAF[[II]]230, Milk Growth, Histone H2b, Histone H2a, cell cycle regulator, Roles, HsT17436, Xmad3, madh3-A, Concepts, TGFbeta receptor binding, Formal Social Controls, signal transduction by protein phosphorylation, MADH3, gamma sarcoglycan, hSMAD3, thymus nucleic acid, DNA methylation maintenance, Gene Expressions, TFIID TAF250, cel, cell sheath, DNA methylation, DNA Methylomes, Social, activin, TGF-beta receptor binding, malignant neoplasm, Role Concepts, inhibin, Mothers against DPP homolog 3, Histone H5, gamma-sarcoglycan, Histone H4, Histone H7, Malignancies, Double-Stranded DNA, deoxyribonucleic acids, DNAn, Histone H1, single organism signaling, Histone H3, Tumors, mamma, dTAF[[II]]230, Methylomes, SG-gamma, lamina, TGF-beta, signal transduction by conformational transition, TAF200, Double-Stranded, TAFII-250, TAF250/230, results, signal transduction by trans-phosphorylation, Programs, (Deoxyribonucleotide)n+m, signaling cascade, TAFII250, Benign, Role Concept, Lobe of mammary gland, Role, XSmad3, Genetic Materials, sarcoglycan, desoxyribose nucleic acid, Methylome, Genetic Material, hMAD-3, mad3, transforming growth factor beta receptor anchoring activity, Platelet Transforming Growth Factor, Control, Benign Neoplasms, mMad3, 6720416L16Rik, Controls, CG17603, gamma (35kDa dystrophin-associated glycoprotein), TAF[[II]], Malignant Neoplasms, HSPC193, DMDA, signaling pathway, Taf250, Material, SR3-5, 35kD dystrophin-associated glycoprotein, ds DNA, Cistron, DNA, other neoplasm, Regulation, Methylation, TAF230, DNA Methylome, Malignant Neoplasms., Regulations, LDS1C, mammary region, d230, SGCG_HUMAN, DNS, (Deoxyribonucleotide)n, JV15-2, Neoplasms, Benign Neoplasm, Gene, Bone-Derived Transforming Growth Factor, dTAFII250, Malignant, EfW1, TYPE, Deoxyribonucleic acids, Bone Derived Transforming Growth Factor, DAGA4, Mad3, Deoxyribonucleic Acid, dmTAF1, Taf230, SMAD 3, 35DAG, Growth Factor, MAM, gamma-SG, SCG3, Histone H3.3, Smad 3, TAF250, Taf200, dTAF[[II]]250, Genetic, Malignancy, cell, ligand, layer, mammary part of chest, Double Stranded, Taf1p, Deoxyribonucleic acid, Expressions, Neoplasias, dTAF250, signalling pathway, MAD homolog 3, AU022421, signal transduction by cis-phosphorylation, Smad3, Expression, (Deoxyribonucleotide)m, TAF, Methylations, Cancer, TAF[[II]]250, Malignant Neoplasm, 35 kDa dystrophin-associated glycoprotein, Formal Social Control, DNAn+1, Madh3, l(3)84Ab, Factor, BG:DS00004.13, LDS3, Brustdruese, Cistrons, Histone, Cell, SGCG, LGMD2C, dTAF230, Concept, MT, Social Control, 1810009F10Rik, p230, Neoplasm, TAF[[II]]250/230, transforming growth factor beta receptor ligand, TFIID, ds-DNA, signalling cascade, Taf[[II]]250, transforming growth factor beta, primary cancer, TAF[[II]]230, distinct, DMDA1, Epigenomes, Lobe of breast, TAF[II]250, Cancers, transforming growth factor beta ligand binding to type II receptor, malignant tumor, Histone H1(s), DmelCG17603, signalling process, SCARMD2, sheath of cells, Desoxyribonukleinsaeure, layer of cells, regulation, Neoplasia, breast, TAF1falseAzaTargeted bisulfite sequencing2017-07-26 15:39:29EGAD00010000868960626686634EGAC00001000407EGAS00001001570