Regulation of NF-kappaB activity through lysine monomethylation of p65.
NF-kappaB is a key activator of inflammatory and immune responses with important pathological roles in cancer, heart disease, and autoimmune diseases. Transcriptional activity of NF-kappaB is regulated by different posttranslational modifications. Here, we report a novel mechanism of NF-kappaB regulation through lysine monomethylation by SET9 methyltransferase. Set9 specifically methylates p65 at lysine 37. Both TNFalpha and IL-1beta treatments induced methylation of p65. Methylated p65 is restricted to the nucleus and this modification regulates the promoter binding of p65. Moreover, Set9 mediated methylation of p65 is required for the expression of a subset of NF-kappaB target genes in response to TNFalpha stimulation.
Division of Biology, California Institute of Technology, 330 Braun, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Chee-Kwee
CK
Ea
David
D
Baltimore
D000818:Animals; D002460:Cell Line; D019175:DNA Methylation; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human