Skip to main content

Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation

Author(s): Zhou, Linjiao; Holt, Matthew T.; Ohashi, Nami; Zhao, Aishan; Müller, Manuel M.; et al

To refer to this page use:
Abstract: Ubiquitylation of histone H2B at lysine 120 (H2B-Ub), a post-translational modification first discovered in 1980, plays a critical role in diverse nuclear processes including the regulation of transcription and DNA damage repair. Herein, we use a suite of protein chemistry methods to explore how H2B-Ub stimulates hDot1L-mediated methylation of histone H3 on lysine 79 (H3K79me). By using semisynthetic ‘designer’ chromatin containing H2B-Ub bearing a site-specifically installed photocrosslinker, here we report an interaction between a functional hotspot on ubiquitin and the N-terminus of histone H2A. Our biochemical studies indicate that this interaction is required for stimulation of hDot1L activity and leads to a repositioning of hDot1L on the nucleosomal surface, which likely places the active site of the enzyme proximal to H3K79. Collectively, our data converge on a possible mechanism for hDot1L stimulation in which H2B-Ub physically ‘corrals’ the enzyme into a productive binding orientation.
Publication Date: 2-Feb-2016
Electronic Publication Date: 2-Feb-2016
Citation: Zhou, Linjiao, Holt, Matthew T., Ohashi, Nami, Zhao, Aishan, Müller, Manuel M., Wang, Boyuan, Muir, Thomas W. (2016). Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation. Nature Communications, 7 (10589 - 10589. doi:10.1038/ncomms10589
DOI: doi:10.1038/ncomms10589
EISSN: 2041-1723
Pages: 10589-1 - 10589-9
Type of Material: Journal Article
Journal/Proceeding Title: Nature Communications
Version: Final published version. This is an open access article.

Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.