A novel histone methyltransferase, Kodo7 has histone H3-K9 methyltransferase activity and induces apoptotic cell death

초록

Evolutionary conserved SET domains were originally identified in three Drosophila proteins: Suppressor of variegation (Sur(var)3—9), Enhancer of zeste (E(z)), and the Trithorax. SET domain-containing proteins presents the activity of methylation to histone lysine residues. Based on research of SET-domain containing proteins, a novel histone methyltransferase (HMTase) was identified, cloned from mouse cells and named Kodo7. Kodo7 contains a SET domain and post-SET domain, but lack the pre-SET domain. For characterization of Kodo7, we performed HMTase assay, lysine specificity, localization study, and cell viability test. Histone methyltransferse activity was confirmed with immunoprecipitated GST-Kodo7 and the H3-K9 lysine specificity was determined in vivo. Localization study of Kodo7 has shown that Kodo7 is colocalized with his tones in nucleus. Apoptosis-related assay revealed that overexpression of Kodo7 induced cell death, probably through caspase—3 activation. H3-K9 methylation is connected with cell silencing and transcriptional repression. Our results show that the increased Kodo7 involve the cell silencing and cell death (apoptosis) through H3K9-methylation.