Activation and regulation of H2B-Ubiquitin-dependent histone methyltransferases

Evan J Worden; Cynthia Wolberger

doi:10.1016/j.sbi.2019.05.009

Activation and regulation of H2B-Ubiquitin-dependent histone methyltransferases

Curr Opin Struct Biol. 2019 Dec:59:98-106. doi: 10.1016/j.sbi.2019.05.009. Epub 2019 Jun 21.

Authors

Evan J Worden¹, Cynthia Wolberger²

Affiliations

¹ Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: cwolberg@jhmi.edu.

Abstract

Covalent modifications of histone proteins regulate a wide variety of cellular processes. Methylation of histone H3K79 and H3K4 is associated with active transcription and is catalyzed by Dot1L and Set1, respectively. Both Dot1L and Set1 are activated by prior ubiquitination of histone H2B on K120 in a process termed 'histone crosstalk'. Recent structures of Dot1L bound to a ubiquitinated nucleosome revealed how Dot1L is activated by ubiquitin and how Dot1L distorts the nucleosome to access its substrate. Structures of Dot1L-interacting proteins have provided insight into how Dot1L is recruited to sites of active transcription. Cryo-EM and crystallographic studies of the complex of proteins associated with Set1 (COMPASS), uncovered the architecture of COMPASS and how Set1 is activated upon complex assembly.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Binding Sites
Enzyme Activation
Histone Methyltransferases / chemistry
Histone Methyltransferases / metabolism*
Histones / chemistry
Histones / metabolism*
Models, Molecular
Molecular Conformation
Protein Binding
Structure-Activity Relationship
Ubiquitin / chemistry
Ubiquitin / metabolism*

Substances

Histones
Ubiquitin
Histone Methyltransferases

Grants and funding

R35 GM130393/GM/NIGMS NIH HHS/United States