Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators
Copyright policy )Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators
The closely related transcription factors (TFs), estrogen receptors ERα and ERβ, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing breast cancer cells with ERα, ERβ, or both receptors as a model system to define the basis for differing response specification by related TFs, we show that these TFs and their key coregulators, SRC3 and RIP140, generate overlapping as well as unique chromatin‐binding and transcription‐regulating modules. Cistrome and transcriptome analyses and the use of clustering algorithms delineated 11 clusters representing different chromatin‐bound receptor and coregulator assemblies that could be functionally associated through enrichment analysis with distinct patterns of gene regulation and preferential coregulator usage, RIP140 with ERβ and SRC3 with ERα. The receptors modified each other's transcriptional effect, and ERβ countered the proliferative drive of ERα through several novel mechanisms associated with specific binding‐site clusters. Our findings delineate distinct TF‐coregulator assemblies that function as control nodes, specifying precise patterns of gene regulation, proliferation, and metabolism, as exemplified by two of the most important nuclear hormone receptors in human breast cancer.
- University of Illinois at Urbana Champaign United States
- University of Illinois Urbana-Champaign United States
- University of Illinois System United States
- Agency for Science, Technology and Research Singapore
- Biomedical Research Council Singapore
Medicine (General), genetic association, gene cluster, Nuclear Receptor Coactivator 3, estrogen receptors α and β, nuclear protein, transcription factor GATA 3, Medicine and Health Sciences, genetics, Protein Interaction Maps, Biology (General), transcription factor, mitogen activated protein kinase, breast tumor, article, Adaptor Proteins, Life Sciences, Nuclear Proteins, gene control, gene expression regulation, Genomics, receptor interacting protein 140, Chromatin, Nuclear Receptor Interacting Protein 1, Gene Expression Regulation, Neoplastic, female, priority journal, protein protein interaction, Multigene Family, NCOA3 protein, Female, transcription regulation, Corrigendum, signal transduction, Signal Transduction, 570, QH301-705.5, proliferation, 610, Breast Neoplasms, signal transducing adaptor protein, Article, adipogenesis, R5-920, estrogen receptor alpha, coregulator usage, Cell Line, Tumor, genomics, Estrogen Receptor beta, Humans, controlled study, human, multigene family, steroid receptor coactivator 3, Adaptor Proteins, Signal Transducing, Cell Proliferation, estrogen receptor beta, binding site, human cell, genetic transcription, tumor cell line, Signal Transducing, Estrogen Receptor alpha, enzyme activation, hepatocyte nuclear factor 3alpha, cell proliferation, gene expression, chromatin, metabolic regulation, gene regulation, Transcriptome, transcriptome, metabolism
Medicine (General), genetic association, gene cluster, Nuclear Receptor Coactivator 3, estrogen receptors α and β, nuclear protein, transcription factor GATA 3, Medicine and Health Sciences, genetics, Protein Interaction Maps, Biology (General), transcription factor, mitogen activated protein kinase, breast tumor, article, Adaptor Proteins, Life Sciences, Nuclear Proteins, gene control, gene expression regulation, Genomics, receptor interacting protein 140, Chromatin, Nuclear Receptor Interacting Protein 1, Gene Expression Regulation, Neoplastic, female, priority journal, protein protein interaction, Multigene Family, NCOA3 protein, Female, transcription regulation, Corrigendum, signal transduction, Signal Transduction, 570, QH301-705.5, proliferation, 610, Breast Neoplasms, signal transducing adaptor protein, Article, adipogenesis, R5-920, estrogen receptor alpha, coregulator usage, Cell Line, Tumor, genomics, Estrogen Receptor beta, Humans, controlled study, human, multigene family, steroid receptor coactivator 3, Adaptor Proteins, Signal Transducing, Cell Proliferation, estrogen receptor beta, binding site, human cell, genetic transcription, tumor cell line, Signal Transducing, Estrogen Receptor alpha, enzyme activation, hepatocyte nuclear factor 3alpha, cell proliferation, gene expression, chromatin, metabolic regulation, gene regulation, Transcriptome, transcriptome, metabolism
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