长非编码RNALHX1-DT通过H2A.Z介导的LHX1转录激活来调节心肌细胞分化
Qi Yu1,2, Benzhi Cai1,3, Yong Zhang1
1Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China.
iScience
|November 9, 2023
概括
一种新的长非编码RNA,LHX1-DT,通过与PHF6.6相互作用来调节早期心肌细胞分化. 它有助于在LHX1基因促销器的基因突变H2A.Z和H2A的交换.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 长非编码RNAs (lncRNAs) 是基因表达的关键调节者.
- 在心肌细胞分化中,lncRNA介导调节的机制尚不清楚.
研究的目的:
- 为了识别和描述参与早期心肌细胞分化中的新型lncRNAs.
- 阐明LHX1-DT在调节心肌细胞发育中的分子机制.
主要方法:
- 使用表达形状的 lncRNAs 的识别.
- 功能性研究涉及基因淘汰和过度表达在人类胚胎干细胞 (hESCs).
- 染色体免疫沉降和RNA结合蛋白相互作用试验.
主要成果:
- 在早期心肌细胞分化过程中,LHX1-DT是一种核局部的lncRNA,在早期心肌细胞分化过程中暂时升调.
- LHX1-DT与PHF6进行物理相互作用,并在LHX1促进体中调解H2A.Z/H2A交换.
- 过度表达LHX1拯救了LHX1-DT淘汰细胞中的分化表型,证实了LHX1作为下游目标.
结论:
- LHX1-DT是心肌细胞分化的关键调节者.
- LHX1-DT采用一种表观遗传机制,涉及质子变体交换来控制LHX1的表达.
- 这项研究揭示了心脏发育中的新型调节途径.
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