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Wnt信号激活诱导CTCF结合和循环形成在基因的cis调节元件的目标基因
Anna Nordin1,2,3, Chaitali Chakraborty4,5, Mattias Jonasson6,2
1Wallenberg Centre for Molecular Medicine, Linköping University, SE-581 83 Linköping, Sweden; claudio.cantu@liu.se anna.nordin@liu.se silvia.remeseiro@umu.se.
Genome research
|June 23, 2025
概括
Wnt信号激活新的CTCF结合部位,影响3D基因组组织和基因表达. 这揭示了CTCF在调节Wnt通路中的新角色.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
背景情况:
- Wnt信号对于发育和恒常状态至关重要.
- β-catenin (CTNNB1) 激活通过TCF/LEF转录因子驱动目标基因表达.
- 基因调节涉及3D基因组结构,但Wnt对它的影响还未得到充分研究.
研究的目的:
- 调查Wnt信号对CTCF和凝聚力的影响,这是关键的3D基因组组织者.
- 确定由Wnt监管的新型CTCF绑定站点.
- 探索Wnt介导的3D基因组重组的功能后果.
主要方法:
- 染色体免疫沉测序 (ChIP-seq) 用于识别CTCF结合部位.
- 分析Wnt监管场所的凝聚力和TCF/LEF占用率.
- 测试对β-catenin的依赖性.
- 3D基因组结构分析 (例如,Hi-C) 来检测循环变化.
主要成果:
- 发现了新的Wnt刺激的CTCF结合位点 (RUW位点).
- RUW 站点表现出 CTCF,cohesin 和 TCF/LEF 的共同占用,它们依赖于β-catenin.
- 在Wnt激活时观察到β-catenin和CTCF的同位化.
- 证明扰乱RUW部位会影响目标基因调节.
- 在CTCF-bound循环中展示了全基因组的改变,表明了3D基因组重组.
结论:
- Wnt信号诱导特定的CTCF绑定事件 (RUW站点).
- 在Wnt路径介导的3D基因组组织中,CTCF发挥着重要作用.
- 这项研究揭示了CTCF在Wnt信号传输中的新型调节功能.
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