Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity.
Evolutionary conserved SET domains were originally identified in three Drosophila proteins: suppressor of variegation (Su (var) 3-9), enhancer of zeste (E(z)), and the trithorax. Some of the SET-domain containing proteins have been known to elicit methylation of histone lysine residues. Based on a search for SET-domain containing proteins using bioinformatic tools, we identified and subsequently named a novel SET domain as WHISTLE, that has histone methyltransferase (HMTase) activity. To characterize WHISTLE, we performed an HMTase assay, mass spectrometric analysis, lysine specificity, and transfection assays. Mass spectrometric and immunoblot analysis revealed that WHISTLE di-methylates H3K4 and di-, and tri-methylates H3K27 of histones. Overexpression of WHISTLE repressed transcription of the SV40 promoter. Our results suggest that WHISTLE is a novel SET domain containing a protein with specific H3K4 and H3K27 HMTase activity.
Kim
Sung Mi
SM
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea.
Kee
Hae Jin
HJ
Eom
Gwang Hyeon
GH
Choe
Nak Won
NW
Kim
Ji Young
JY
Kim
Young Soo
YS
Kim
Seong Ki
SK
Kook
Hoon
H
Kook
Hyun
H
Seo
Sang Beom
SB