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非コーディングRNAの転写は,ハンド2発現と心臓の発達を制御する
Kelly M Anderson1,2, Douglas M Anderson1,2, John R McAnally1,2
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature
|November 4, 2016
まとめ
Hand2遺伝子の発現を維持するために,新しい長い非コーディングRNA,Uperhand (Uph) が不可欠であり,心臓発達の重要な要因である. Uphの転写が妨げられ,マウスの心臓に重篤な欠陥があり,胚は死に至る.
科学分野:
- 発達生物学
- 遺伝学
- 分子生物学
背景:
- HAND2は心臓の発達を制御する重要な転写因子です.
- その発現は,H3K27acの改変によってマークされた強化剤によって制御されます.
- HAND2の調節不良は 心臓の欠陥と胚の死亡を引き起こします
研究 の 目的:
- Hand2発現を調節する新しい長い非コーディングRNA,上手 (Uph) の役割を調査する.
- UphがHand2増強剤の活性に影響を与えるメカニズムを解明する.
- Uphの機能障害が心臓の発達に及ぼす影響を理解する.
主な方法:
- マウスモデルにおけるUph転写とそのハンド2発現への影響の分析
- 超強化シグネチャーの維持におけるUphの役割の調査
- Hand2増強器のロクスを通してRNAポリメラーゼIIの延長を評価する.
- Uphの転写阻害を受けたマウスの表型分析
主要な成果:
- ハンド2の超強化シグネチャーを維持するには,Uphのトランスクリプションが必要です.
- Uphのトランスクリプションを遮断するが,成熟したトランスクリプトをノックダウンし,Hand2発現を廃止した.
- Uphの破壊は右心室の低増殖とマウスの胚死亡を引き起こした.
- Uphは,Hand2増強部を通してRNAポリメラーゼIIの延長を促進する.
結論:
- Uph-Hand2の規制パートナーシップは,非コーディングRNAによる遺伝子発現の制御のための新しいメカニズムを強調しています.
- 異なった非コーディングトランスクリプションは,発達に不可欠な許容性クロマチンの環境を確立することができます.
- この発見は,心臓の発達と遺伝子調節における lncRNA の役割を理解するための意味を持つ.
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