Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators
Abstract 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 respon...
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| Format: | Article |
| Language: | English |
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Springer Nature
2013-06-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2013.28 |
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| author | Zeynep Madak‐Erdogan Tze‐Howe Charn Yan Jiang Edison T Liu John A Katzenellenbogen Benita S Katzenellenbogen |
| author_facet | Zeynep Madak‐Erdogan Tze‐Howe Charn Yan Jiang Edison T Liu John A Katzenellenbogen Benita S Katzenellenbogen |
| author_sort | Zeynep Madak‐Erdogan |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-f68048a262e64fbc98d5940ec13e2b2a |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2013-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-f68048a262e64fbc98d5940ec13e2b2a2025-08-20T04:02:44ZengSpringer NatureMolecular Systems Biology1744-42922013-06-019111910.1038/msb.2013.28Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulatorsZeynep Madak‐Erdogan0Tze‐Howe Charn1Yan Jiang2Edison T Liu3John A Katzenellenbogen4Benita S Katzenellenbogen5Department of Molecular and Integrative Physiology, and Cell and Developmental Biology, University of Illinois at Urbana‐ChampaignDepartment of Bioengineering, University of Illinois at Urbana‐ChampaignDepartment of Molecular and Integrative Physiology, and Cell and Developmental Biology, University of Illinois at Urbana‐ChampaignThe Genome Institute of SingaporeDepartment of Chemistry, University of Illinois at Urbana‐ChampaignDepartment of Molecular and Integrative Physiology, and Cell and Developmental Biology, University of Illinois at Urbana‐ChampaignAbstract 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.https://doi.org/10.1038/msb.2013.28coregulator usageestrogen receptors α and βgene regulationmetabolismproliferation |
| spellingShingle | Zeynep Madak‐Erdogan Tze‐Howe Charn Yan Jiang Edison T Liu John A Katzenellenbogen Benita S Katzenellenbogen Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators Molecular Systems Biology coregulator usage estrogen receptors α and β gene regulation metabolism proliferation |
| title | Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators |
| title_full | Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators |
| title_fullStr | Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators |
| title_full_unstemmed | Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators |
| title_short | Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators |
| title_sort | integrative genomics of gene and metabolic regulation by estrogen receptors α and β and their coregulators |
| topic | coregulator usage estrogen receptors α and β gene regulation metabolism proliferation |
| url | https://doi.org/10.1038/msb.2013.28 |
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