2012 Fiscal Year Final Research Report
Histone demethylase Jmjd1a as a regulator of glycolipid metabolism
Project/Area Number |
21687013
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Molecular biology
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Research Institution | The University of Tokyo |
Principal Investigator |
INAGAKI Takeshi 東京大学, 先端科学技術研究センター, 特任准教授 (10507825)
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Research Collaborator |
SAKAI Juro 東京大学, 先端科学技術研究センター, 教授 (80323020)
SHINKAI Yoichi 理化学研究所, 主任研究員 (20211972)
TACHIBANA Makoto 京都大学, ウィルス研究所, 准教授 (80303915)
ABURATANI Hiroyuki 東京大学, 先端科学技術研究センター, 教授 (10202657)
KODAMA Tatsuhiko 東京大学, 先端科学技術研究センター, 教授 (90170266)
KAWAMURA Takeshi 東京大学, 先端科学技術研究センター, 助教 (70306835)
OKAMURA Hitoshi 京都大学, 薬学研究科, 教授 (60158813)
DOI Masao 京都大学, 薬学研究科, 准教授 (20432578)
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Project Period (FY) |
2009 – 2012
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Keywords | エピゲノム / ヒストン脱メチル化酵素 / Jmjd1a / 糖脂質代謝調節 |
Research Abstract |
Jmjd1a (also known as Jhdm2a and KDM3a) catalyzes removal of H3K9 mono- and dimethylation. We established JMJD1a deficient mice (JMJD1A -/-) and discovered that the mice develop adult onset obesity, hypertriglyceridemia, hypercholesterolemia, and insulin insensitivity, that are hallmarks of metabolic syndrome. To investigate the molecular mechanism of Jmjd1a working machinery, we sought to elucidate Jmjd1a target genes and working complex using techniques of chromatin immonoprecipitation and mass spectrometry. We raised monoclonal antibodies against mouse and human Jmjd1a protein prepared by baculovirus expression system. ChIP sequence using Jmjd1a antibody as well as methylated histone antibodies showed a specific binding region which codes a retrotransposon. Whole cell extracted protein from HeLa cells was immunoprecipitated using the established Jmjd1a antibodies and the precipitated protein complex was analyzed using shotgun mass spectrometry. Interestingly, a series of splicing factors and sin3a complex forming proteins appeared in the list of shotgun proteomics. It is also elucidated that there is a functional phosphorylated site in Jmjd1a. Our result indicates that Jmjd1a regulates gene transcription through changing the chromatin formation.
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[Journal Article] Dynamic change of the chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of HIF1 and KDM3A2012
Author(s)
Mimura I, Nangaku M, Kanki Y, Tsutsumi S, Inoue T, Kohro T, Yamamoto S, Fujita T, Shimamura T, Suehiro JI, Taguchi A, Kobayashi M, Tanimura K, Inagaki T,Tanaka T, Hamakubo T, Sakai J,Aburatani H, Kodama T, Wada Y.
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Journal Title
Mol. Cell. Biol
Volume: 32
Pages: 3018-3032
DOI
Peer Reviewed
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