Histone H2B ubiquitination in transcription regulation
Abstract
Post-translational modifications of histones play a central role in regulating all cellular processes requiring access to DNA. Cross-talk between histone modifications, in which one histone modification regulates deposition of a second, provides an additional layer of regulation and specificity. Monoubiquitinated histone H2B-K120 (humans; K123 in yeast) is a hallmark of actively transcribed genes that plays multiple roles in activating transcription. Our structural studies have revealed how H2B is specifically ubiquitinated and deubiquitinated, as well as the mechanism by which H2B ubiquitination stimulates the enzymes that methylate histone H3K4 and H3K79, two other marks of actively-transcribed genes. H2B ubiquitination also regulates access to the nucleosome acidic patch, a hotspot for interactions with other chromatin-modifying enzymes, and our studies have provided insights into the underlying mechanism. We will also present work on identifying novel inhibitors of USP22, an H2B deubiquitinating enzyme subunit of the SAGA coactivator.
