Transcriptomics

Dataset Information

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Development of a selective CDK7 covalent inhibitor reveals predominant cell cycle phenotype


ABSTRACT: The relationship between promoter proximal transcription factor-associated gene expression and super-enhancer-driven transcriptional programs are not well-defined. Some level of their distinct genomic occupancy may suggest a mechanism with specific target gene control. We explored the transcriptional and functional interrelationship between E2F transcription factors and BET transcriptional co-activators in multiple myeloma. Global chromatin analysis reveals distinct regulatory axes for E2F and BETs, with E2F predominantly localized to active gene promoters of growth/proliferation genes and BETs disproportionately at enhancer- regulated tissue specific genes. Depletion of E2F selectively down-regulates its regulatory axis and is generally synergistic with BET inhibition. In vivo, combined inhibition of BETs and E2F strongly reduces tumor growth, implicating E2F as a myeloma dependency that is potently leveraged with BET inhibition.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124607 | GEO | 2019/01/04

REPOSITORIES: GEO

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