ヒトのプリインプラント胚および多能細胞における内在レトロウイルスの再活性化
Edward J Grow1, Ryan A Flynn2, Shawn L Chavez3
1Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|April 22, 2015
まとめ
ヒト内生レトロウイルス (HERVK) は,DNA低甲基化とOCT4.4により,人間の発達初期に発現します. RecのようなHERVKタンパク質は,ウイルス感染を抑制し,胚の発達に影響を与えます.
科学分野:
- ゲノミクスゲノミクスとは
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学について
背景:
- 固有のレトロウイルス (ERV) は,ヒトゲノムの8%を占める古代のレトロウイルス配列です.
- 人間内生レトロウイルスK (HERVK) は,タンパク質をコードする遺伝子を無傷のまま保持し,最近獲得されたものです.
- HERVKは典型的には静止されているが,特定の病理および早期発症において活発である.
研究 の 目的:
- 人間の胚形成中にHERVK発現を調節するメカニズムを調査する.
- 初期の発達と宿主防御におけるHERVKタンパク質の機能的役割を決定する.
主な方法:
- DNAメチル化とOCT4 (POU5F1) トランザクティベーションの分析.
- ヒト胚のサンプルにおけるHERVK転写とタンパク質の検出.
- HERVKタンパク質の活性を評価するために,多能細胞系を用いた機能検査.
主要な成果:
- DNAヒポメチル化とOCT4は,ヒト胚形成中にHERVKの発現を相乗的に活性化します.
- HERVKの転写は,8細胞段階から芽細胞発達の過程で起こります.
- HERVKウイルスのような粒子とGagタンパク質は,ヒトの芽細胞に存在します.
- HERVKアクセサリータンパク質 Recは,細胞表面 IFITM1 を強化し,ウイルス感染を抑制する.
- Recは細胞のRNAと相互作用し,リボソームの占有率を調節する.
結論:
- HERVKの発現は,正常なヒト胚形成の過程で制御されるプロセスです.
- HERVKタンパク質は,発達初期に先天的免疫と宿主-病原体相互作用に役割を果たす可能性があります.
- レトロウイルスの要素は,宿主細胞経路と発達過程に影響を与えることができます.
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