胚外血統の表遺伝的制限は,体内の癌への移行を反映している
Zachary D Smith1,2,3, Jiantao Shi4,5, Hongcang Gu1
1Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Nature
|September 30, 2017
まとめ
哺乳類のDNAメチル化パターンは発達初期に異なっており,胚外組織は独特に発達遺伝子プロモーターをメチル化している. このエピジェネティック・ランドスケープは,がんで再活性化され,発育と腫瘍発生の関連性を示唆しています.
科学分野:
- エピジェネティクス
- 発達生物学
- 癌 生物学
背景:
- 哺乳類におけるDNAメチル化パターンの確立と破壊は,発達と癌にとって極めて重要ですが,そのメカニズムは不明のままです.
- カノニカルソマティックDNAメチレーションは胚の発達初期に確立され,様々な癌で変化します.
研究 の 目的:
- マウスの植入前の発達過程で全局的なDNAリメチル化を分析する.
- 胚と胚外血統におけるDNAメチル化の違いを理解する.
- 癌のメチル化パターンと 発達のエピジェネティックの関連性を調べる
主な方法:
- ネズミの植入前の胚から初期のエピブラストと胚外皮への全局的なDNAリメチル化の分析.
- DNAメチル化によるゲノム分布分析
- 胚性および胚外組織とヒトがんのメチル化パターンの比較
主要な成果:
- 胚と胚外血統の間のDNAメチル化パターンの有意な差異
- 胚外エピジェノームは,発達レギュレータのCpG島プロモーターでde novoメチル化を示す.
- これらのプロモーターはヒトの癌でもメチル化され,共用の表遺伝的メカニズムを示唆しています.
結論:
- 胚外組織の進化には,胚の組織におけるポリコンブ群のタンパク質調節とは異なる遺伝子抑制のためのDNAメチル化が含まれている可能性があります.
- この表遺伝的決定は決定的であり,特定の表遺伝的共同因子を含む.
- 発達の遺伝子プロモーターの癌メチル化は,潜伏した発達の表遺伝子プログラムの再活性化を表すかもしれない.
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