阶段分离指导基因体核体的无处不在
Laura D Gallego1, Maren Schneider1, Chitvan Mittal2
1Max Perutz Labs, Medical University of Vienna, Vienna Biocenter Campus (VBC), Vienna, Austria.
Nature
|March 28, 2020
概括
酵母Bre1和Rad6酶使用液态相分离来单基因组H2B. 这一过程产生了色素反应室,增强了基因体的无处不在性,并可能影响人类的神经疾病.
科学领域:
- 分子生物学
- 表观遗传学
- 生物化学
背景情况:
- 基因转录中,素H2B单化是至关重要的,由Bre1 (E3泛联酶) 和Rad6 (E2酶) 催化.
- 通过Bre1和Rad6实现跨基因体的过程性H2B无处不在的机制尚不清楚.
- 之前的模型表明酶可能与RNA聚合酶II一起传播, 但这并不能完全解释观察到的模式.
研究的目的:
- 通过基因体阐明基因素H2B无处不在的机制.
- 调查液态相分离在H2B无处不在化过程中的作用.
- 了解染色体相关酶如何实现增强的催化活性.
主要方法:
- Bre1-Rad6-Lge1系统的生物化学复制
- 对脚手架蛋白 Lge1 的相分离特性进行分析.
- 使用酵母遗传学的体内研究来评估Lge1的凝结物形成区域的功能.
主要成果:
- 支架蛋白Lge1驱动液态相分离,与Bre1形成分层凝结物.
- 这些凝结物招募Rad6和核基质,显著加速H2B无处不在.
- 在活体中,Lge1的凝聚物形成区域对于H2B无处不在至关重要.
结论:
- 基因组修饰酶的分层凝聚剂作为染色体相关反应室,增强沿基因体的催化活性.
- 这种相分离机制为转录过程中的表观遗传调节提供了新的理解.
- 人类细胞的相分离受损可能与神经疾病有关.
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