Li Zhao, Yiqi Wang, Anbalagan Jaganathan, Yifei Sun, Ning Ma, Ning Li, Xinye Han, Xueying Sun, Huanfa Yi, Shibo Fu, Fangbin Han, Xue Li, Kunhong Xiao, Martin J Walsh, Lei Zeng, Ming-Ming Zhou, Ka Lung Cheung
BRD4 is a well-recognized transcriptional activator, but how it regulates gene transcriptional repression in a cell type-specific manner has remained elusive. In this study, we report that BRD4 works with Polycomb repressive complex 2 (PRC2) to repress transcriptional expression of the T-helper 2 (Th2)-negative regulators Foxp3 and E3-ubiqutin ligase Fbxw7 during lineage-specific differentiation of Th2 cells from mouse primary naïve CD4+ T cells. Brd4 binds to the lysine-acetylated-EED subunit of the PRC2 complex via its second bromodomain (BD2) to facilitate histone H3 lysine 27 trimethylation (H3K27me3) at target gene loci and thereby transcriptional repression...
January 31, 2023: EMBO Journal