Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators

Zeynep Madak-Erdogan, Tze Howe Charn, Yan Jiang, Edison T. Liu, John A. Katzenellenbogen, Benita S Katzenellenbogen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number201328
JournalMolecular Systems Biology
Volume9
DOIs
StatePublished - Jan 1 2013

Fingerprint

Estrogen Receptor
Transcription factors
Transcription Factor
Genomics
Estrogen Receptors
Receptor
Transcription Factors
transcription factors
Genes
Breast Cancer
Gene expression
breast neoplasms
Gene
genomics
Gene Regulation
Chromatin
Breast Neoplasms
receptors
chromatin
genes

Keywords

  • coregulator usage
  • estrogen receptors a and b
  • gene regulation
  • metabolism
  • proliferation

ASJC Scopus subject areas

  • Medicine(all)
  • Information Systems
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics
  • Applied Mathematics

Cite this

Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators. / Madak-Erdogan, Zeynep; Charn, Tze Howe; Jiang, Yan; Liu, Edison T.; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.

In: Molecular Systems Biology, Vol. 9, 201328, 01.01.2013.

Research output: Contribution to journalArticle

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