Post-translational modifications of histones play a central role in regulating all cellular processes requiring access to DNA. Monoubiquitinated histone H2B-K120 is a hallmark of actively transcribed genes that plays multiple roles in activating transcription, while monoubiquitinated histone H2A-K119 is abundant in heterochromatin, which is transcriptionally silent. Our structural studies have revealed how histone H2B is specifically ubiquitinated and deubiquitinated, and ubiquitinated H2B stimulates histone methylation. We have also shown how ubiquitin can regulate access to the nucleosome acidic patch, a hotspot for interactions with other chromatin-modifying enzymes. I will also discuss recent studies of a histone kinase that has an unusual mode of binding nucleosomes.
