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

Linjiao Zhou, Matthew T. Holt, Nami Ohashi, Aishan Zhao, Manuel M. Müller, Boyuan Wang and Tom W. Muir ()
Additional contact information
Linjiao Zhou: Princeton University
Matthew T. Holt: Laboratory of Synthetic Protein Chemistry, The Rockefeller University
Nami Ohashi: Princeton University
Aishan Zhao: Princeton University
Manuel M. Müller: Princeton University
Boyuan Wang: Princeton University
Tom W. Muir: Princeton University

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10589 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10589

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10589

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().