揭开复杂的核受体元素 (cNRE) 的进化起源,这是一个需要在心房中优先表达的 cis 调节模块
Luana Nunes Santos1,2,3, Ângela Maria Sousa Costa1, Martin Nikolov2
1Brazilian Biosciences National Laboratory (LNBio), Brazilian Center of Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.
Communications biology
|April 4, 2024
概括
心脏肌肉素基因表达是室偏差的,慢肌肉素重链III (SMyHC III) 特别是在心房. 这种心房偏好是由一个可能源自古老病毒的调节元件控制的.
科学领域:
- 心血管生物学 心血管生物学
- 分子遗传学 分子遗传学
- 发展生物学 发展生物学
背景情况:
- 心室对肌肉蛋白有不同的需求:心房需要缓慢的肌肉蛋白来保持储存功能,而心室需要快速的肌肉蛋白来有效送.
- 肌肉蛋白基因表达失衡有助于先天性心脏功能障碍,突显了室特异性调节的重要性.
- 了解控制肌蛋白表达的 cis 调节机制对于破译心室专业化至关重要.
研究的目的:
- 确定负责心脏中缓慢肌肉素重链III (SMyHC III) 基因室偏差表达的调节输入.
- 为了阐明底层的分子机制,心房特异性SMyHC III基因表达.
- 研究心室特定调节元件的进化起源.
主要方法:
- 长SMyHC III促进体的计算和分子剖析.
- 在斑马鱼和小鼠中使用转基因的功能分析.
- 比较基因组学来追踪调节元素的进化历史.
主要成果:
- 该SMyHC III促进器是由一个32个基对复杂的核受体元素 (cNRE) 编排的.
- 在cNRE中,心房特异性表达是由心房激活和心室抑制动机的组合驱动的.
- 对比基因组学表明cNRE可能起源于一种内源性病毒元素,该元素被整合到祖先宿主的生殖系中.
结论:
- 心室偏差基因表达,以SMyHC III为例,是通过组合性cis调节输入实现的.
- 这项研究揭示了一条新的进化途径,用于产生心室特异性基因调节,涉及病毒元素.
- 这些发现提供了对心脏发育的遗传基础和潜在的潜在机制潜在的先天性心脏病的见解.
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