ヒトの植入前の胚のDNAメチル化ダイナミクス
Zachary D Smith1, Michelle M Chan2, Kathryn C Humm3
11] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5].
Nature
|August 1, 2014
まとめ
哺乳類の父性ゲノムは,発達初期に脱メチル化され,ヒトの研究では,マウスと比較して,特に遺伝子体と種固有のプロモーターにおいて,保存され,異なった表遺伝的調節が明らかにされています.
科学分野:
- エピジェネティクスと発達生物学
- ゲノミクスとバイオインフォマティクス
背景:
- 哺乳類のDNAメチル化は,CpG部位で通常安定しており,受精後の父親のゲノムのダイナミックな再プログラミングとは対照的です.
- ネズミの脱メチル化はよく研究されているが,ヒトの初期の胚の表遺伝的景観は,比較分析のために直接測定を必要とする.
研究 の 目的:
- ヒトの植入前の発達と胚性幹細胞の派生に関するゲノムスケールのDNAメチル化マップを作成する.
- 人間のエピジェネティック再プログラミングを確立されたマウスモデルと比較し,保存された特徴と異なる特徴を特定する.
主な方法:
- ゲノムスケールDNAメチレーションマッピング
- ヒトの移植前の胚と胚性幹細胞の分析
- マウスモデルによる比較ゲノミクスとマウスモデルによる比較ゲノミクス
主要な成果:
- ヒトの早期発達では,一時的なグローバル低メチル化が示され,残基メチル化維持は主に遺伝子体で行われます.
- 母性メチレーションは,ヒトにおける種特有のCpG島プロモーターを標的とし,既知のマウスインプリントとは異なる.
- レトロトランポゾン調節は多様性を示し,母体から胚の発現パターンに変化します.
結論:
- 父のゲノム脱メチル化は,哺乳類の早期発達の保存された特徴である.
- 人間とマウスの初期の胚の表遺伝的景観は,保存されたダイナミクスと種特有の規制の分岐の両方を示しています.
- 独特な表遺伝的調節モードは,哺乳類の間で父親のゲノム再プログラミングを特徴づける.
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