@article{2658, keywords = {Humans, Gene Expression Regulation, Enzymologic, Protein Binding, Models, Molecular, Protein Conformation, Methylation, Histones, Methyltransferases, Nucleosomes, Ubiquitinated Proteins, Histone-Lysine N-Methyltransferase}, author = {Linjiao Zhou and Matthew Holt and Nami Ohashi and Aishan Zhao and Manuel M{\"u}ller and Boyuan Wang and Tom Muir}, title = {Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation.}, 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 {\textquoteright}designer{\textquoteright} 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 {\textquoteright}corrals{\textquoteright} the enzyme into a productive binding orientation.

}, year = {2016}, journal = {Nat Commun}, volume = {7}, pages = {10589}, month = {2016 Feb 02}, issn = {2041-1723}, doi = {10.1038/ncomms10589}, language = {eng}, }