LINE1-Nucleolin パートナーシップは,早期発達とESCのアイデンティティを規制する
Michelle Percharde1, Chih-Jen Lin2, Yafei Yin3
1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell
|June 26, 2018
まとめ
LINE1のレトロトランスポーザンは 早期の発達に不可欠です 重要な遺伝子とRNA合成を制御し 胚幹細胞の自己再生と胚の発達を可能にします
科学分野:
- ゲノミクス
- 発達生物学
- 分子生物学
背景:
- LINE1レトロトランポゾンを含む移植可能な要素は,哺乳類のゲノムの大部分を構成する.
- LINE1要素は,しばしば有害とみなされるにもかかわらず,逆説的に発達初期に高度に発現します.
- 胚性幹細胞と 初期の胚形成における 精密な機能は ほとんど未知のままです
研究 の 目的:
- ネズミの胚性幹細胞 (ESC) と移植前の胚におけるLINE1レトロトランスポーソンの重要な役割を調査する.
- LINE1が初期発達の過程で遺伝子発現と細胞過程に影響を与える分子メカニズムを解明する.
主な方法:
- LINE1RNAがESCにおける核の支柱としての役割を分析する.
- LINE1 RNAによるNucleolinとKap1/Trim28の採用を調査する.
- LINE1のダックス抑制とrDNA結合への影響を評価する.
- 胚におけるrRNA合成と発達の過程におけるLINE1の必要性を評価する.
主要な成果:
- LINE1RNAはESCの核基として機能し,核リンとKap1/Trim28をマスターレギュレータDuxを抑制する.
- LINE1 RNAは,ヌクレオリンとKap1のrDNAへの結合を促進し,それによってrRNA合成とESCの自己更新を促進する.
- LINE1 RNAは,Duxサイレンシング,rRNA合成,および胚の2細胞段階からの移行に不可欠である.
結論:
- LINE1 RNAは,転写,発達の効能,そしてESCの自己更新を調節する上で不可欠な役割を果たします.
- LINE1 RNA,Nucleolin,Kap1,および周辺核染色体間の重要なパートナーシップは,重要な発達プロセスに存在する.
- LINE1のレトロトランスポーソンは単なるジャンクDNAではなく,哺乳類の早期発達における重要な機能要素です.
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