BRD4 is a newly characterized transcriptional regulator that represses autophagy and lysosomal function

Abstract

As a member of the bromodomain and extraterminal (BET) family, BRD4 (bromodomain containing 4) can bind to acetylated histones and transcription factors, and is also able to recruit various transcriptional regulators. Previous studies have shown that BRD4 mainly plays a positive role in cell growth and cell cycle progression. In a recent study conducted by Sakamaki et al., the authors found that BRD4 acts as a transcriptional repressor in regulating macroautophagy/autophagy and lysosome gene expression, via binding to the histone lysine methyltransferase EHMT2/G9a. The oncoprotein BRD4-NUTM1/NUT also helps block autophagy and lysosome functions. A knockdown of BRD4 allows the retention of MTOR activity during starvation and significantly undermines starvation-induced cell death. However, BRD4 repression only contributes to stimulus-dependent autophagy and aggrephagy, and is not involved in other types of selective autophagy. Taken together, the newly reported repressive role of BRD4 in autophagy adds to our understanding of how autophagy and lysosome functions are regulated at the transcriptional level.