Dichotomous engagement of HDAC3 activity governs inflammatory responses.

ABSTRACT: The histone deacetylases (HDACs) are a superfamily of chromatin-modifying enzymes that silence transcription through the modification of histones. Among them, HDAC3 is unique in that interaction with nuclear receptor corepressors 1 and 2 (NCoR1/2) is required to engage its catalytic activity^1-3. However, global loss of HDAC3 also results in the repression of transcription, the mechanism of which is currently unclear^4-8. Here we report that, during the activation of macrophages by lipopolysaccharides, HDAC3 is recruited to activating transcription factor 2 (ATF2)-bound sites without NCoR1/2 and activates the expression of inflammatory genes through a non-canonical mechanism. By contrast, the deacetylase activity of HDAC3 is selectively engaged at ATF3-bound sites that

SUBMITTER: Nguyen HCB 

PROVIDER: S-EPMC7725280 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature