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ヒストンH3K36me2およびH3K36me3はマウス卵子におけるDNMT3A依存的DNAメチル化に必須なクロマチンプラットフォームを形成する

矢野, 誠一 YANO, Seiichi ヤノ, セイイチ 九州大学

2022.12.31

概要

哺乳類の卵子では、DNMT3A-DNMT3L複合体を介したDNAメチル化の確立が生殖と発生に重要である。マウスの卵子では、転写活性領域でのみ高度のメチル化が起き、他の領域では中程度から低レベルのメチル化が起きる。ヒストン修飾H3K36me3は転写領域での高度のメチル化を媒介するが、他の領域でメチル化を誘導するヒストン修飾は不明であった。我々は、マウス卵子において、H3K36me2がX染色体へ高度に集積しており、常染色体全体に広く分布していることを明らかにした。H3K36me2を低下させると、中程度のメチル化領域でのDNAメチル化が選択的に影響を受け、X染色体特有のメチル化パターンが常染色体様のパターンに切り替わることがわかった。さらに、H3K36me2とH3K36me3を同時に低下させると、DNMT3Aを欠損した時と同程度までDNAメチル化が低下することも見いだした。したがって、この2つのヒストン修飾は、マウス卵子においてDNMT3A依存的なDNAメチル化を誘導するために不可欠なクロマチンプラットフォームを協調的に形成していることがわかった。

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