Glucocorticoid Receptor: MegaTrans Switching Mediates Repression of ER?-Regulated Transcriptional Program
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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 ? (ER?) in breast cancer development remain poorly understood. Here we report that, in breast cancer cells, liganded GR represses a large ER?-activated transcriptional program by binding, in trans, to ER?-occupied enhancers. This abolishes effective activation of these enhancers and their cognate target genes, and it leads to the inhibition of ER?-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:This SuperSeries is composed of the SubSeries listed below.
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