TAD边界删除会导致与PITX2相关的心脏电气和结构缺陷
Manon Baudic1, Hiroshige Murata2, Fernanda M Bosada3
1Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, F-44000, Nantes, France.
Nature communications
|April 20, 2024
概括
删除CTCF结合点会破坏3D染色体组织,导致一种新的心脏疾病. 这项研究揭示了改变的拓关联域 (TADs) 如何影响基因调节并导致孟德尔病.
科学领域:
- 遗传学 是一个遗传学.
- 基因组学就是基因组学.
- 心血管生物学 心血管生物学
背景情况:
- 三维染色体组织,包括拓关联域 (TAD) 和调节循环,对于组织特异性基因调节至关重要.
- 在人类孟德尔病,特别是心脏病中,受损色素组织的作用仍然在很大程度上未被探索.
研究的目的:
- 调查3D染色体组织缺陷与新型心脏实体之间的联系.
- 确定这种新的孟德尔心脏疾病背后的遗传和分子机制.
主要方法:
- 鉴定患有与特定染色体缺失相关的新型心脏病的家庭.
- 创建一个模拟人类删除的小鼠模型来研究其影响.
- 在患者衍生的心肌细胞中进行染色质构成测定,以分析TAD变化.
主要成果:
- 在七个患有新心脏疾病的家庭中,在4q25染色体上发现了两个CTCF结合点的异构缺失.
- 删除诱导了拓关联域 (TAD) 融合和染色体构造重塑.
- 一个小鼠模型重复了人类的表型,显示了心脏中异常调节的对状同居体转录因子2 (PITX2) 表达.
结论:
- 删除CTCF结合部位导致TAD重塑,并导致一种新的自体主导门德尔心脏疾病.
- 3D染色体组织的破坏是人类遗传性心脏病的致病机制.
更多相关视频
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
9.7K
10:13Multi-Photon Time Lapse Imaging to Visualize Development in Real-time: Visualization of Migrating Neural Crest Cells in Zebrafish Embryos
Published on: August 9, 2017
7.6K
相关概念视频
Teratogenicity
2.4K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
2.4K
Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
