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非编码RNA的转录控制Hand2表达和心脏发育
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
概括
一种新的长非编码RNA,Uperhand (Uph),对于维持Hand2基因表达至关重要,这是心脏发育的关键因素. 在小鼠中,Uph转录的破坏导致严重的心脏缺陷和胚胎死亡.
科学领域:
- 发育生物学
- 遗传学
- 分子生物学
背景情况:
- HAND2是调节心脏发育的关键转录因子.
- 它的表达是由H3K27ac修饰标记的增强剂控制的.
- HAND2的失调会导致心脏缺陷和胚胎死亡.
研究的目的:
- 研究一种新型长非编码RNA (Uph) 在调节Hand2表达中的作用.
- 阐明Uph影响Hand2增强剂活性的机制.
- 了解Uph干扰对心脏发育的功能后果.
主要方法:
- 在小鼠模型中分析Uph转录及其对Hand2表达的影响.
- 调查Uph在维护超级增强器签名中的作用.
- 通过Hand2增强器位置进行RNA聚合酶II延长的评估.
- 具有Uph转录阻塞的小鼠的表型分析.
主要成果:
- 维护Hand2超级增强器的特征需要Uph转录.
- 阻断Uph转录,但没有成熟的转录,取消了Hand2表达.
- 在小鼠中,Uph的干扰导致了右心室低成形和胚胎死亡.
- Uph通过Hand2增强器位置促进RNA聚合酶II的延长.
结论:
- 通过非编码RNA控制基因表达的新机制.
- 不同的非编码转录可以建立对发育至关重要的容许性染色体环境.
- 这一发现对理解心脏发育和lncRNAs在基因调节中的作用有影响.
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