The histone methyltransferase activity of WHISTLE is important for the induction of apoptosis and HDAC1-mediated transcriptional repression.
Posttranslational histone methylation has been correlated with transcriptional regulation. However, the functional significance of methylation of lysine residues of histone remains largely unknown. Previously, we have characterized a novel histone methyltransferase (HMTase), WHISTLE which methylates histone H3-K4 and H3-K27 to repress transcription. In this study, we demonstrated that WHISTLE can induce apoptotic cell death through caspase-3 activation and that HMTase activity is important for the apoptosis induction. Deletion mapping analysis elicited that N-terminus PWWP region is required for HMTase activity by interacting with putative associating factors. Point mutant analysis revealed that SET domain cysteine 297 is a critical residue for the HMTase activity of WHISTLE. WHISTLE repressed transcription through HDAC1 recruitment possibly through the N-terminus region. Our results suggest that HMTase WHISTLE induces apoptosis in an HMTase activity-dependent manner and represses transcription of target genes through HDAC1 recruitment.
Kim
Sung-Mi
SM
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Korea.
Kee
Hae-Jin
HJ
Choe
Nakwon
N
Kim
Ji-Young
JY
Kook
Hoon
H
Kook
Hyun
H
Seo
Sang-Beom
SB
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins; D017354:Point Mutation; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
D009687:Nuclear Proteins; D012097:Repressor Proteins; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C432968:NSD3 protein, human; D053148:Caspase 3; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases