title: Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP.
abstract: G9a is a SET-domain mammalian histone methyltransferase responsible for mono- and dimethylation of lysine 9 in histone H3 (H3K9) at euchromatic regions. Recently we reported that G9a forms a stoichiometric heteromeric complex with another SET-domain-containing molecule, GLP/Eu-HMTase1. Although G9a and GLP can independently methylate H3K9 in vitro, G9a/GLP heteromeric formation seems to be essential for their function as a euchromatic H3K9 methyltransferase in vivo. To further elucidate how G9a/GLP-mediated histone methylation and transcriptional regulation are controlled, we purified and characterized G9a complexes from mouse embryonic stem cells. We identified a novel G9a/GLP-associating zinc finger molecule named Wiz that can interact with G9a and GLP independently but is more stable in the G9a/GLP heteromeric complexes. Interestingly, Wiz small inhibitory RNA knocks down not only Wiz but also G9a. GLP deficiency also decreases G9a levels, suggesting that the Wiz/G9a/GLP tri-complex may protect G9a from degradation and that Wiz plays a major role in G9a/GLP heterodimer formation. Furthermore, amino acid sequence analysis of Wiz predicted two potential CtBP binding sites, and indeed CtBP binding to Wiz and association of CtBP with the Wiz/G9a/GLP complex was observed. These data indicate that Wiz not only contributes to the stability of G9a but also links the G9a/GLP heteromeric complex to the CtBP co-repressor machinery.
authors.affiliation: Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ueda
authors.forename: Makoto
authors.initials: M
authors.lastname: Tachibana
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D019281:Dimerization; D020868:Gene Silencing; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C119196:Wiz protein, mouse; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; C513479:GLP protein, mouse; D011495:Histone-Lysine N-Methyltransferase