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Glucocorticoid inducton of DDIT4 transcription

ABSTRACT: The hormone stimulated Glucocorticoid Receptor (GR) modulates transcription by interacting with thousands of enhancers and GR binding sites (GBSs) throughout the genome. Here, we examined the effects of GR binding on enhancer dynamics and interrogated the contributions of individual GBSs to the hormone response. Hormone treatment resulted in genome-wide reorganization of the enhancer landscape in breast cancer cells. Upstream of the DDIT4 oncogene, GR bound to four sites constituting a hormone-dependent super enhancer. Three GBSs were required as hormone-dependent enhancers that differentially promoted histone acetylation and transcription frequency and burst size. Conversely, the fourth site suppressed transcription and hormone treatment alleviated this suppression. GR binding within the super enhancer promoted a loop-switching mechanism that allowed interaction of the DDIT4 TSS with the active GBSs. The unique functions of each GR binding site contributed to hormone-induced transcriptional heterogeneity and demonstrate the potential for targeted modulation of oncogene expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173798 | GEO | 2022/01/24

REPOSITORIES: GEO

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