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基于CTCF的强大的染色体结构支持心脏衰竭应激基因反应的表观遗传变化
Dominic Paul Lee1,2, Wilson Lek Wen Tan1,2, Chukwuemeka George Anene-Nzelu1,2
1Genome Institute of Singapore (D.P.L., W.L.W.T., C.G.A.-N., C.J.M.L., C.X.C., Z.T., S.L.N., M.E., M.I.A., S.P., R.S.-Y.F.).
Circulation
|February 6, 2019
概括
基因组
科学领域:
- 基因组学
- 分子生物学
- 心血管研究
背景情况:
- 人类基因组折叠成3D染色体循环,
- 这些环节由CTCF蛋白和凝聚素复合体固定.
- 心脏衰竭涉及与CTCF介导的染色体重组相关的基因表达变化.
研究的目的:
- 独立分析心肌应激反应中的染色体组织变化.
- 研究CTCF在压力期间心脏基因调节中的作用.
主要方法:
- 使用压力过载的小鼠模型 (横向大动脉收缩).
- 产生了心肌细胞特异性CTCF淘汰小鼠.
- 重新分析已发表的心脏小鼠模型数据集.
主要成果:
- 在压力过载期间,心脏染色质结构保持稳定.
- CTCF淘汰几乎取消了所有全球色素循环 (≈99%).
- 基因表达的变化与稳定的染色体结构中的增强剂的基因H3K27- 乙化相关.
结论:
- 整个基因组的染色体结构比以前想象的更加稳定.
- 心肌应激反应依赖于H3K27-乙化动态和基因网络.
- 完整的CTCF循环对于快速准确的应激反应至关重要.
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