| Literature DB >> 27068464 |
Anand S Bhagwat1, Jae-Seok Roe2, Beverly Y L Mok2, Anja F Hohmann2, Junwei Shi3, Christopher R Vakoc4.
Abstract
The bromodomain and extraterminal (BET) protein BRD4 can physically interact with the Mediator complex, but the relevance of this association to the therapeutic effects of BET inhibitors in cancer is unclear. Here, we show that BET inhibition causes a rapid release of Mediator from a subset of cis-regulatory elements in the genome of acute myeloid leukemia (AML) cells. These sites of Mediator eviction were highly correlated with transcriptional suppression of neighboring genes, which are enriched for targets of the transcription factor MYB and for functions related to leukemogenesis. A shRNA screen of Mediator in AML cells identified the MED12, MED13, MED23, and MED24 subunits as performing a similar regulatory function to BRD4 in this context, including a shared role in sustaining a block in myeloid maturation. These findings suggest that the interaction between BRD4 and Mediator has functional importance for gene-specific transcriptional activation and for AML maintenance.Entities:
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Year: 2016 PMID： 27068464 PMCID： PMC4838499 DOI： 10.1016/j.celrep.2016.03.054
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423