凝聚力挤出的能量和生理影响
Laura Vian1, Aleksandra Pękowska1, Suhas S P Rao2
1Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Cell
|May 1, 2018
概括
基因组架构依赖于凝聚性挤出,这是第一次在体内可视化的过程. 这项研究揭示了
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 凝聚蛋白挤出是一种被提议用于哺乳动物基因组结构的机制.
- 在体内可视化和凝聚素挤出的功能影响仍然在很大程度上未知.
研究的目的:
- 在体内可视化凝聚挤出并确定其能量需求.
- 研究凝聚性挤出在基因组结构形成和维护中的作用.
- 探索凝聚力介导的循环和建筑条纹的功能意义.
主要方法:
- 分析基因组结构的超深Hi-C测序.
- 涉及ATP耗尽的实验,以研究凝聚性ATPase的要求.
- 对CTCF独立的循环和架构条纹的分析.
- 研究条纹与调节性DNA元素的相互作用以及它们在转录和重组中的作用.
主要成果:
- 循环域通过需要凝聚性ATPases的过程形成,但在没有能量输入的情况下维持.
- ATP的耗尽导致了许多CTCF独立循环的形成.
- 连接环到整个领域, 连接超级增强器到促进器.
- 条纹在B细胞中促进Igh转录和重组,并且可以在癌症中调节瘤基因.
- 条纹是因染色体转移而引起的热点.
结论:
- 凝聚蛋白挤出对于循环形成至关重要,但不需要维护,需要ATP.
- 在缺少ATP的条件下出现了CTCF独立的循环,突出了替代的监管机制.
- 建筑条纹在基因调节中起着重要作用,并与癌症发展有关.
- 较高的生物可能已经进化了凝聚性挤出以增强转录和重组,这对瘤发生有影响.
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