The histone methyltransferase activity of WHISTLE is important for the induction of apoptosis and HDAC1-mediated transcriptional repression

Abstract

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. (c) 2006 Elsevier Inc. All rights reserved.