A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex

Lauriane Fritsch; Philippe Robin; Jacques R R Mathieu; Mouloud Souidi; Hélène Hinaux; Claire Rougeulle; Annick Harel-Bellan; Maya Ameyar-Zazoua; Slimane Ait-Si-Ali

doi:10.1016/j.molcel.2009.12.017

A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex

Mol Cell. 2010 Jan 15;37(1):46-56. doi: 10.1016/j.molcel.2009.12.017.

Authors

Lauriane Fritsch¹, Philippe Robin, Jacques R R Mathieu, Mouloud Souidi, Hélène Hinaux, Claire Rougeulle, Annick Harel-Bellan, Maya Ameyar-Zazoua, Slimane Ait-Si-Ali

Affiliation

¹ Institut André Lwoff, Centre National de la Recherche Scientifique, FRE2944, Université Paris-Sud, 94800 Villejuif, France.

PMID: 20129054
DOI: 10.1016/j.molcel.2009.12.017

Abstract

Lysine 9 of histone 3 (H3K9) can be mono-, di-, or trimethylated, inducing distinct effects on gene expression and chromatin compaction. H3K9 methylation can be mediated by several histone methyltransferases (HKMTs) that possess mono-, di-, or trimethylation activities. Here we provide evidence that a subset of each of the main H3K9 HKMTs, G9a/KMT1C, GLP/KMT1D, SETDB1/KMT1E, and Suv39h1/KMT1A, coexist in the same megacomplex. Moreover, in Suv39h or G9a null cells, the remaining HKMTs are destabilized at the protein level, indicating that the integrity of these HKMTs is interdependent. The four HKMTs are recruited to major satellite repeats, a known Suv39h1 genomic target, but also to multiple G9a target genes. Moreover, we report a functional cooperation between the four H3K9 HKMTs in the regulation of known G9a target genes. Altogether, our data identify a H3K9 methylation multimeric complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA, Satellite / metabolism
Enzyme Stability
Gene Expression Regulation
HeLa Cells
Histocompatibility Antigens / genetics
Histocompatibility Antigens / metabolism
Histocompatibility Antigens / physiology*
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / metabolism
Histone-Lysine N-Methyltransferase / physiology*
Histones / metabolism*
Humans
Methylation
Methyltransferases / genetics
Methyltransferases / metabolism
Methyltransferases / physiology*
Protein Methyltransferases / genetics
Protein Methyltransferases / metabolism
Protein Methyltransferases / physiology*
Protein Transport
Recombinant Fusion Proteins / metabolism
Repressor Proteins / genetics
Repressor Proteins / metabolism
Repressor Proteins / physiology*

Substances

DNA, Satellite
Histocompatibility Antigens
Histones
Recombinant Fusion Proteins
Repressor Proteins
SUV39H1 protein, human
EHMT1 protein, human
Methyltransferases
Protein Methyltransferases
EHMT2 protein, human
Histone-Lysine N-Methyltransferase
SETDB1 protein, human