H3K4me2/3 modulate the stability of RNA polymerase II pausing
Shibin Hu, Aixia Song, Linna Peng, Nan Tang, Zhibin Qiao, Zhenning Wang, Fei Lan, Fei Chen
Abstract
Modifications of histones are intricately linked with the regulation of gene expression, having demonstrated roles in various physiological processes and pathogenesis. Methylation of histone H3 lysine 4 (H3K4) implemented by the COMPASS family is enriched at promoters and associated cis-regulatory elements, with H3K4 trimethylation (H3K4me3) being a hallmark of active gene promoters. 1 However, the relative contributions of the deposition and removal of H3K4 methylation to transcriptional control remain unclear. We found that rapid depletion of core COMPASS subunits led to a dynamic turnover of H3K4me2 and H3K4me3 that is mediated by KDM5 demethylases. Depleting H3K4me2 and H3K4me3 did not affect TFIID recruitment or initiating RNA polymerase II (Pol II) but instead reduced levels of paused Pol II, which could be attributed to increased enrichment of the Integrator-PP2A complex (INTAC).