Format

Send to

Choose Destination
J Biol Chem. 2015 Oct 23;290(43):26088-102. doi: 10.1074/jbc.M115.654459. Epub 2015 Sep 3.

A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin.

Author information

1
From the Carolina Institute for Developmental Disabilities, Department of Cell Biology and Physiology, and the Department of Genetics, Curriculum in Bioinformatics and Computational Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
2
the Department of Genetics and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
3
the Center for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina 27599.
4
the Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan 49503.
5
the Laboratoire Epigénétique et Destin Cellulaire, UMR7216, CNRS, Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France.
6
the Lineberger Comprehensive Cancer Center, the Curriculum in Genetics and Molecular Biology, and the Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
7
the Department of Structural and Chemical Biology, the Department of Oncological Sciences, and the Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
8
the Department of Genetics, the Lineberger Comprehensive Cancer Center, the Department of Pediatrics, and the Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and.
9
the Department of Biochemistry and Molecular Biology and the Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202.
10
the Center for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina 27599, pattenden@unc.edu.

Abstract

G9a and GLP lysine methyltransferases form a heterodimeric complex that is responsible for the majority of histone H3 lysine 9 mono- and di-methylation (H3K9me1/me2). Widely interspaced zinc finger (WIZ) associates with the G9a-GLP protein complex, but its role in mediating lysine methylation is poorly defined. Here, we show that WIZ regulates global H3K9me2 levels by facilitating the interaction of G9a with chromatin. Disrupting the association of G9a-GLP with chromatin by depleting WIZ resulted in altered gene expression and protein-protein interactions that were distinguishable from that of small molecule-based inhibition of G9a/GLP, supporting discrete functions of the G9a-GLP-WIZ chromatin complex in addition to H3K9me2 methylation.

KEYWORDS:

chromatin modification; chromatin regulation; protein methylation; transcription; transcription coregulator

PMID:
26338712
PMCID:
PMC4646261
DOI:
10.1074/jbc.M115.654459
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center