The MSX1 homeoprotein recruits G9a methyltransferase to repressed target genes in myoblast cells.
Although the significance of lysine modifications of core histones for regulating gene expression is widely appreciated, the mechanisms by which these modifications are incorporated at specific regulatory elements during cellular differentiation remains largely unknown. In our previous studies, we have shown that in developing myoblasts the Msx1 homeoprotein represses gene expression by influencing the modification status of chromatin at its target genes. We now show that genomic binding by Msx1 promotes enrichment of the H3K9me2 mark on repressed target genes via recruitment of G9a histone methyltransferase, the enzyme responsible for catalyzing this histone mark. Interaction of Msx1 with G9a is mediated via the homeodomain and is required for transcriptional repression and regulation of cellular differentiation, as well as enrichment of the H3K9me2 mark in proximity to Msx1 binding sites on repressed target genes in myoblast cells as well as the developing limb. We propose that regulation of chromatin status by Msx1 recruitment of G9a and other histone modifying enzymes to regulatory regions of target genes represents an important means of regulating the gene expression during development.
Department of Urology and Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
Jingqiang
J
Wang
Cory
C
Abate-Shen
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D019175:DNA Methylation; D006649:Histocompatibility Antigens / Q000235:genetics* / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D051957:MSX1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D006649:Histocompatibility Antigens; D051957:MSX1 Transcription Factor; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase