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R567位点的CTCF点突变通过三维基因组重排和转录失调破坏小鼠心脏发育。

CTCF Point Mutation at R567 Disrupts Mouse Heart Development via 3D Genome Rearrangement and Transcription Dysregulation.

作者信息

Ren Huawei, Zhong Hongxin, Zhang Jie, Lu Yuli, Hu Gongcheng, Duan Weixun, Ma Ning, Yao Hongjie

机构信息

College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.

State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

出版信息

Cell Prolif. 2025 Apr;58(4):e13783. doi: 10.1111/cpr.13783. Epub 2024 Dec 16.

DOI:10.1111/cpr.13783
PMID:39682078
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11969252/
Abstract

CTCF plays a vital role in shaping chromatin structure and regulating gene expression. Clinical studies have associated CTCF mutations with congenital developmental abnormalities, including congenital cardiomyopathy. In this study, we investigated the impact of the homozygous CTCF-R567W (Ctcf ) mutation on cardiac tissue morphogenesis during mouse embryonic development. Our results reveal significant impairments in heart development, characterised by ventricular muscle trabecular hyperplasia and reduced ventricular cavity sizes. We also observe a marked downregulation of genes involved in sarcomere assembly, calcium ion transport, and mitochondrial function in heart tissues from homozygous mice. Furthermore, the Ctcf mutation disrupts CTCF's interaction with chromatin, resulting in alterations to topologically associating domain (TAD) structure within specific genomic regions and diminishing crucial promoter-enhancer interactions necessary for cardiac development. Additionally, we find that the heterozygous CTCF-R567W (Ctcf ) mutation significantly compromises cardiac contractility in 8-week-old mice. This study elucidates the mechanism by which the CTCF-R567W mutation hampers cardiac development, underscoring the essential role of CTCF-R567 in embryonic heart development and maturation.

摘要

CTCF在塑造染色质结构和调节基因表达方面发挥着至关重要的作用。临床研究已将CTCF突变与先天性发育异常相关联，包括先天性心肌病。在本研究中，我们调查了纯合CTCF-R567W（Ctcf ）突变对小鼠胚胎发育期间心脏组织形态发生的影响。我们的结果显示心脏发育存在显著缺陷，其特征为心室肌小梁增生和心室腔大小减小。我们还观察到纯合小鼠心脏组织中参与肌节组装、钙离子转运和线粒体功能的基因明显下调。此外，Ctcf 突变破坏了CTCF与染色质的相互作用，导致特定基因组区域内的拓扑相关结构域（TAD）结构改变，并削弱了心脏发育所需的关键启动子-增强子相互作用。此外，我们发现杂合CTCF-R567W（Ctcf ）突变显著损害8周龄小鼠的心脏收缩力。本研究阐明了CTCF-R567W突变阻碍心脏发育的机制，强调了CTCF-R567在胚胎心脏发育和成熟中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/ef5d66693264/CPR-58-e13783-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/3cb4ae4c6025/CPR-58-e13783-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/ec3bb0b19cd0/CPR-58-e13783-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/c10fd1667f96/CPR-58-e13783-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/36b8f983ef5e/CPR-58-e13783-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/ef5d66693264/CPR-58-e13783-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/3cb4ae4c6025/CPR-58-e13783-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/ec3bb0b19cd0/CPR-58-e13783-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/c10fd1667f96/CPR-58-e13783-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/36b8f983ef5e/CPR-58-e13783-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/11969252/ef5d66693264/CPR-58-e13783-g003.jpg

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本文引用的文献

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CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment.CTCF 突变 R567 导致 3D 基因组重排和神经发育异常的发育障碍。
Nat Commun. 2024 Jul 1;15(1):5524. doi: 10.1038/s41467-024-49684-1.
2
Enhancer-promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1.在急性 CTCF、cohesin、WAPL 或 YY1 缺失的情况下，增强子-启动子相互作用和转录在很大程度上得以维持。
Nat Genet. 2022 Dec;54(12):1919-1932. doi: 10.1038/s41588-022-01223-8. Epub 2022 Dec 5.
3
CTCF shapes chromatin structure and gene expression in health and disease.
CTCF 塑造健康和疾病状态下的染色质结构和基因表达。
EMBO Rep. 2022 Sep 5;23(9):e55146. doi: 10.15252/embr.202255146. Epub 2022 Aug 22.
4
CTCF functions as an insulator for somatic genes and a chromatin remodeler for pluripotency genes during reprogramming.CTCF 在重编程过程中作为体细胞基因的绝缘子和多能性基因的染色质重塑因子发挥作用。
Cell Rep. 2022 Apr 5;39(1):110626. doi: 10.1016/j.celrep.2022.110626.
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Plotgardener: cultivating precise multi-panel figures in R.Plotgardener：在 R 中种植精确的多面板图形。
Bioinformatics. 2022 Mar 28;38(7):2042-2045. doi: 10.1093/bioinformatics/btac057.
6
The assembly, regulation and function of the mitochondrial respiratory chain.线粒体呼吸链的组装、调节和功能。
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7
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