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マウスのCpG島で獲得された表遺伝子シグネチャの世代間継承
Yuta Takahashi1, Mariana Morales Valencia1, Yang Yu2
1Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, Suite 300, San Diego, CA 92121, USA.
Cell
|February 8, 2023
まとめ
この研究では DNAメチル化による遺伝子の変化は ネズミの世代から世代へと受け継がれます これらのエピジェネティックの変化は代謝に影響を与え 世代を超えて受け継がれます
科学分野:
- エピジェネティクス
- 哺乳類の遺伝学
- 発達生物学
背景:
- 哺乳類における世代間表遺伝子遺伝は十分に確立されていない.
- DNAメチル化パターンは遺伝子発現と細胞機能に影響を与える.
研究 の 目的:
- 哺乳類のDNAメチル化による世代を超えた遺伝を証明する.
- 既得の表遺伝的変異とその現象的効果の遺伝性を調査する.
主な方法:
- 標的型CpG島 (CGI) メチル化によるDNAメチル化編集されたマウス胚性幹細胞 (ESC) の生成
- CGIメチル化による代謝関連の遺伝子 (アンキリンリピートドメイン26および低密度リポタンパク質受容体) の静止.
- メチル化ESCの微量注射によるマウスの生成と,世代間のフェノタイプの特徴とメチル化パターンの分析.
主要な成果:
- ESCでは,特定のCGIのメチル化とサイレンスが達成されました.
- メチル化されたESCから派生したマウスは異常な代謝現象を示した.
- 獲得したCGIメチル化および関連する表型特性は,複数の世代に渡って安定的に伝達された.
- 遺伝性メチレーションは親の生殖細胞で再プログラムされ,移植後の子孫で再確立された.
結論:
- この研究は,哺乳類におけるDNAメチル化による世代間表遺伝の証拠を提供する.
- 遺伝された表遺伝的変異はフェノタイプに影響し,生殖線の再プログラムと再確立の対象となります.
- この発見は進化生物学と 非遺伝的な人間の病気の理解に 影響を及ぼします
キーワード:
CpG島DNAメチル化DNAメチレーションで編集されたマウスDNAメチレーションで編集されたマウスのES細胞生物学的な進化エピゲノムエピミュテーション肥満世代を超えたエピジェネティック遺伝メタボリックフェノタイプの伝播さらに関連する動画
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