Glucocorticoid Receptor: MegaTrans Switching Mediates Repression of ER?-Regulated Transcriptional Program
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE81512 | GEO | 2017/03/01
SECONDARY ACCESSION(S): PRJNA321833
REPOSITORIES: GEO
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Project description:The molecular mechanisms underlying the opposing functions of glucocorticoid receptors (GRs) and estrogen receptor α (ERα) in breast cancer development remain poorly understood. Here we report that, in breast cancer cells, liganded GR represses a large ERα-activated transcriptional program by binding, in trans, to ERα-occupied enhancers. This abolishes effective activation of these enhancers and their cognate target genes, and it leads to the inhibition of ERα-dependent binding of components of the MegaTrans complex. Consistent with the effects of SUMOylation on other classes of nuclear receptors, dexamethasone (Dex)-induced trans-repression of the estrogen E2 program appears to depend on GR SUMOylation, which leads to stable trans-recruitment of the GR-N-CoR/SMRT-HDAC3 corepressor complex on these enhancers. Together, these results uncover a mechanism by which competitive recruitment of DNA-binding nuclear receptors/transcription factors in trans to hot spot enhancers serves as an effective biological strategy for trans-repression, with clear implications for breast cancer and other diseases.
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Project description:Glucocorticoid Receptor: MegaTrans Switching Mediates Repression of ER?-Regulated Transcriptional Program
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Project description:The mechanisms underlying GR-dependent inhibition of ERα-regulated gene activation programs at the global genomic level have been poorly understood. We found the binding of GR in trans on ERα-activated enhancers results in gene and enhancer repression by disassembling the MegaTrans Complex.
2017-03-01 | GSE81511 | GEO
Project description:The mechanisms underlying GR-dependent inhibition of ERα-regulated gene activation programs at the global genomic level have been poorly understood. We found the binding of GR in trans on ERα-activated enhancers results in gene and enhancer repression by disassembling the MegaTrans Complex.
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