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KAKEN_15K09296seika.pdf
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TET2によるエピゲノム制御を介したミネラルコルチコイド活性制御と高血圧発症機構
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TET2 ニ ヨル エピゲノム セイギョ オ カイシタ ミネラルコルチコイド カッセイ セイギョ ト コウケツアツ ハツショウ キコウ
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TET2 ni yoru epigenomu seigyo o kaishita minerarukoruchikoido kassei seigyo to kōketsuatsu hatsushō kikō
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The role of TET2 in mineralocorticoid receptor mediated transcription through epigenetic mechanisms and development of hypertension
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小林, 佐紀子
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コバヤシ, サキコ
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Kobayashi, Sakiko
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慶應義塾大学・医学部(信濃町)・特任講師
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Research team head
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科研費研究者番号 : 80383727
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2018
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科学研究費補助金研究成果報告書
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2017
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ミネラルコルチコイド受容体(MR)のエピゲノムを介した転写活性化の分子メカニズムの解明のため, 新規MR相互作用因子スクリーニングで得られた因子のうち, 脱メチル化酵素であるten-eleven translocation 2(TET2)に注目した。TET2のknock downによりアルドステロンによるMR標的遺伝子のSGK1とENaCのmRNAレベルの増加の抑制が認められ, TET2はMRの転写活性を促進する転写促進因子であることが示唆された。他のMRスクリーニングで同定されたエピゲノムに関連する因子についても転写共役因子である可能性が示唆された。
To elucidate the mechanisms of MR mediated transcription through epigenetic mechanisms, we decided to focus on one of demethylase, ten-eleven translocation 2(TET2) among MR interacting proteins which were obtained in our MR-interacting protein-screening. Knock down of TET2 suppressed the transcriptional activation of MR target genes, SGK1 and ENaC, by aldosterone and it was suggested that TET2 transactivates MR mediated transcription. Other proteins related to epigenetic mechanisms which were obtained in our screening were also shown to control MR mediated transcription.
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研究種目 : 基盤研究(C)(一般)
研究期間 : 2015～2017
課題番号 : 15K09296
研究分野 : 内分泌内科
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