A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex.
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.
Institut André Lwoff, Centre National de la Recherche Scientifique, FRE2944, Université Paris-Sud, 94800 Villejuif, France.
Lauriane
L
Fritsch
Philippe
P
Robin
Jacques R R
JR
Mathieu
Mouloud
M
Souidi
Hélène
H
Hinaux
Claire
C
Rougeulle
Annick
A
Harel-Bellan
Maya
M
Ameyar-Zazoua
Slimane
S
Ait-Si-Ali
D004276:DNA, Satellite / Q000378:metabolism; D004795:Enzyme Stability; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D004276:DNA, Satellite; D006649:Histocompatibility Antigens; D006657:Histones; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C407843:SUV39H1 protein, human; C455847:EHMT1 protein, human; D008780:Methyltransferases; D011496:Protein Methyltransferases; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; C454062:SETDB1 protein, human