Post-translational modifications of histones play a central role in regulating all cellular processes requiring access to DNA. 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. I will also present work on identifying novel inhibitors of USP22, an H2B deubiquitinating enzyme subunit of the SAGA coactivator.
The focus of my research has been to develop tools for measuring mechanical forces and apply these tools to gain mechanistic insights into fundamental biological processes, such as cellular and tissue homeostasis. In this talk I will highlight recent work using nanobody-based force sensors to measure mechanical forces on nuclear lamins, and how these sensors can be used to study force transmission across other cytoskeletal structures. I will also present work examining how forces are applied onto the nuclear pore complex and how these forces could regulate nuclear-cytosolic transport. Lastly, I will discuss our work studying the role of mechanical forces in 3D epithelial structures, using MDCK cysts as a model system.
Last update: 3/22/2024, Ralf Bundschuh