A Jumonji (Jarid2) Protein Complex Represses cyclin D1 Expression by Methylation of Histone H3-K9

• Published in: The Journal of biological chemistry Vol. 284; no. 2; pp. 733 - 739
• Main Authors: Shirato, Haruki, Ogawa, Satoko, Nakajima, Kuniko, Inagawa, Masayo, Kojima, Mizuyo, Tachibana, Makoto, Shinkai, Yoichi, Takeuchi, Takashi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09-01-2009; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Cell Line; Cyclin D1 - genetics; Cyclin D1 - metabolism; Gene Expression Regulation; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Histones - chemistry; Histones - genetics; Histones - metabolism; Humans; Methylation; Mice; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Promoter Regions, Genetic - genetics; Protein Binding; Protein Methyltransferases - genetics; Protein Methyltransferases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M804994200

Covalent modifications of histone tails have critical roles in regulating gene expression. Previously, we identified the jumonji (jmj, Jarid2) gene, the jmjC domain, and a Jmj family. Recently, many Jmj family proteins have been shown to be histone demethylases, and jmjC is the catalytic domain. However, Jmj does not have histone demethylase activity because the jmjC domain lacks conserved residues for binding to cofactors. Independently of these studies, we previously showed that Jmj binds to the cyclin D1 promoter and represses the transcription of cyclin D1. Here, we show the mechanisms by which Jmj represses the transcription of cyclin D1. We found that a protein complex of Jmj had histone methyltransferase activity toward histone H3 lysine 9 (H3-K9). We also found that Jmj bound to the H3-K9 methyltransferases G9a and GLP. Expression of Jmj recruited G9a and GLP to the cyclin D1 promoter and increased H3-K9 methylation. Inactivation of both G9a and GLP, but not of only G9a, inhibited the methylation of H3-K9 in the cyclin D1 promoter and repression of cyclin D1 expression by Jmj. These results suggest that Jmj methylates H3-K9 and represses cyclin D1 expression through G9a and GLP, and that Jmj family proteins can regulate gene expression by not only histone demethylation but also other histone modification.