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ネズミのメタステーブルエピアレルの識別,特徴化,遺伝性:非遺伝的遺伝への影響
Anastasiya Kazachenka1, Tessa M Bertozzi1, Marcela K Sjoberg-Herrera2
1Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
Cell
|November 21, 2018
まとめ
レトロトランスポゾンも,内皮のA粒子 (IAP) のように,マウスのDNAメチル化が変化し,遺伝子発現と毛皮の色に影響する. これらのエピジェネティック状態は受精後にリセットされますが,次の世代で再確立されます.
科学分野:
- エピジェネティクス
- ゲノミクス
- 発達生物学
背景:
- リトロトランスポゾンには,内皮のA粒子 (IAP) 要素が含まれ,マウンのゲノムの重要な部分を占めています.
- エピジェネティックメカニズムは通常,レトロトランスポゾン活動を抑制する.
- アグウティ活性の黄色 (Avy) 位置は,遺伝的に同一の個体で変異性DNAメチル化を示し,世代を超えて遺伝される変異性毛色の発現につながります.
研究 の 目的:
- Avyロカスに類似した表遺伝子特性を有するマウリンの内A粒子 (IAP) 要素を識別する.
- これらの特定されたIAPの表遺伝的行動と規制の可能性を調査する.
- 世代を超えて変数IAPメチル化状態の遺伝パターンと再プログラミングを検証する.
主な方法:
- C57BL/6Jマウスの全ゲノムスクリーニングで,変異性表遺伝子状態のIAPを特定する.
- 特定のIAP位置でのDNAメチル化分析
- 隣接遺伝子のプロモーターとしてのIAPの役割の評価
- 授精後のIAPメチル化再プログラムと世代間の分析
主要な成果:
- 多数のC57BL/6Jマウイン IAPは,Avyロカスに類似した変数DNAメチル化で特定されました.
- それぞれのIAPは個体内で安定したメチル化状態を維持したが,個体によって異なる.
- これらのIAPは,隣接する遺伝子のプロモーターとしてめったに作用せず,そのメチル化は局所特異的であった.
- 変異的にメチル化されたIAPの横の領域は,CTCFの結合部位のために濃縮された.
- IAPのメチル化状態は受精後に再プログラムされ,次の世代で再確立された.
結論:
- 変性メチル化IAPはネズミのゲノムで一般的であり,局所特有の表遺伝子調節を示す.
- IAPにおけるメタステーブルな表遺伝子状態の再プログラムと再確立は,非遺伝的遺伝モデルの一般化性を挑戦しています.
- これらの発見は,レトロトランポゾンのダイナミックな表遺伝的性質と,フェノタイプの変化を生成するにおけるその役割を強調しています.
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