JQ1, a bromodomain inhibitor, suppresses Th17 effectors by blocking p300-mediated acetylation of RORγt.

ABSTRACT:

Background and purpose

Th17 cells play critical roles in chronic inflammation, including fibrosis. Histone acetyltransferase p300, a bromodomain-containing protein, acetylates RORγt and promotes Th17 cell development. The bromodomain inhibitor JQ1 was shown to alleviate Th17-mediated pathologies, but the underlying mechanism remains unclear. We hypothesized that JQ1 suppresses the response of Th17 cells by impairing p300-mediated acetylation of RORγt.

Experimental approach

The effect of JQ1 on p300-mediated acetylation of RORγt was investigated in HEK293T (overexpressing Flag-p300 and Myc-RORγt) and human Th17 cells through immunoprecipitation and western blotting. To determine the regions of p300 responsible for JQ1-mediated suppression of HAT activity, we performed HAT ass

SUBMITTER: Wang X 

PROVIDER: S-EPMC7280011 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature