Bromodomain inhibitor JQ1 reversibly blocks IFN-γ production.

ABSTRACT: As a class, 'BET' inhibitors disrupt binding of bromodomain and extra-terminal motif (BET) proteins, BRD2, BRD3, BRD4 and BRDT, to acetylated histones preventing recruitment of RNA polymerase 2 to enhancers and promoters, especially super-enhancers, to inhibit gene transcription. As such, BET inhibitors may be useful therapeutics for treatment of cancer and inflammatory disease. For example, the small molecule BET inhibitor, JQ1, selectively represses MYC, an important oncogene regulated by a super-enhancer. IFN-γ, a critical cytokine for both innate and adaptive immune responses, is also regulated by a super-enhancer. Here, we show that JQ1 represses IFN-γ expression in TH1 polarized PBMC cultures, CD4+ memory T cells, and NK cells. JQ1 treatment does not reduce activating chromatin marks

SUBMITTER: Gibbons HR 

PROVIDER: S-EPMC6635431 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature