EHMT1 protein binds to nuclear factor-κB p50 and represses gene expression.
Transcriptional homeostasis relies on the balance between positive and negative regulation of gene transcription. Methylation of histone H3 lysine 9 (H3K9) is commonly correlated with gene repression. Here, we report that a euchromatic H3K9 methyltransferase, EHMT1, functions as a negative regulator in both the NF-κB- and type I interferon-mediated gene induction pathways. EHMT1 catalyzes H3K9 methylation at promoters of NF-κB target genes. Moreover, EHMT1 interacts with p50, and, surprisingly, p50 appears to repress the expression of type I interferon genes and genes activated by type I interferons by recruiting EHMT1 to catalyze H3K9 methylation at their promoter regions. Silencing the expression of EHMT1 by RNA interference enhances expression of a subset NF-κB-regulated genes, augments interferon production, and augments antiviral immunity.
Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Chee-Kwee
CK
Ea
ShengLi
S
Hao
Kok Siong
KS
Yeo
David
D
Baltimore
D000818:Animals; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008745:Methylation; D051379:Mice; D008817:Mice, Mutant Strains; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D006657:Histones; D007370:Interferon Type I; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D012097:Repressor Proteins; C073701:Nfkb1 protein, mouse; C455847:EHMT1 protein, human; D011495:Histone-Lysine N-Methyltransferase