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KAKEN_24689037seika.pdf
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心筋細胞特異的発現遺伝子群の統合的調節機構および慢性的疾患発生機序の解明
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シンキン サイボウ トクイテキ ハツゲン イデンシグン ノ トウゴウテキ チョウセツ キコウ オヨビ マンセイテキ シッカン ハッセイ キジョ ノ カイメイ
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Shinkin saibo tokuiteki hatsugen idenshigun no togoteki chosetsu kiko oyobi manseiteki shikkan hassei kijo no kaimei
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Coordinated epigenetic regulation of cell type-specific genes and chronic disease development in cardiomyocytes.
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小田, 真由美
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オダ, マユミ
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Oda, Mayumi
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慶應義塾大学・医学部・助教
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Research team head
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科研費研究者番号 : 80567511
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迫田, 実希
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サコタ, ミキ
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Sakota, Miki
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慶應義塾大学・医学部・研究員
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Research team member
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2014
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科学研究費補助金研究成果報告書
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2013
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本研究計画では各発生段階からの均一な心筋細胞集団からDNAメチル化エピゲノムデータから、細胞種特異的なDNAメチル化エピゲノムの成り立ちについての理解を深めた。結果として、細胞特異的発現遺伝子の一部に、gene body領域での顕著なDNAメチル化変動を経る遺伝子があることを見出した。これら成熟細胞におけるgene body領域の低メチル化状態は転写マシナリーおよびp300の蓄積を伴い、さらに成熟過程における細胞種および発生段階特異的な一過性なDNA脱メチル化中間産物の蓄積と関連している。gene body領域でのDNA脱メチル化プロセスが細胞特異的遺伝子発現に関与している可能性を示した。
In this study, I made several cell type-specific DNA methylation epigenome data of isolated cardiomyocyte populations from several developmental stages and pushed forward understanding of the epigenome in matured cells. I compared the cardiomyocyte epigenome with those of embryonic stem cells and liver, and also with the heart failure cardiac muscle cells. As the result, small subpopulation of genes with remarkable DNA methylation changes in their gene body regions were included in the cell type-specific gene trait. These gene body regions accumulated the transcription machinery and histone acetylation enzyme in the matured cells, and transiently accumulate the derivatives of methyl cytosine demethylation, which implicates the active demethylation process. Our study showed the involvement of the active DNA demethylation process in gene body regions and indicates the possibility that the gene body DNA hypomethylation may stabilize the cell type-specific gene transcription.
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研究種目 : 若手研究(A)
研究期間 : 2012～2013
課題番号 : 24689037
研究分野 : 医歯薬学
科研費の分科・細目 : 内科系臨床医学・循環器内科学
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