通过Chd1和FACT解决转录诱导的六体体-核体复合体
Maik Engeholm1, Johann J Roske2, Elisa Oberbeckmann1
1Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, Göttingen 37077, Germany.
Molecular cell
|September 13, 2024
概括
像Chd1这样的染色体重塑剂在转录过程中解决了六体-核体复合体. 实际上,FACT恢复了基因组二次体,激活了Chd1,以支持RNA聚合酶II的活性.
科学领域:
- 分子生物学分子生物学
- 染色体生物学 染色体生物学
- 生物化学 生物化学
背景情况:
- 在基因转录过程中,依赖ATP的染色质重塑剂和基因素陪伴剂保持核细胞组织.
- RNA聚合酶II (RNAPII) 活动可以破坏核体结构,需要重塑因素.
- 六体体,核体中间体缺少一个组素H2A/H2B二元体,在转录的基因区域形成.
研究的目的:
- 阐明染色体重塑剂Chd1与六体-核体复合体相互作用的机制.
- 确定FACT复合体在调节这些复合体上的Chd1活性中的作用.
- 为在转录过程中对染色质重塑的调节提供结构性见解.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定 Chd1 与六体体-核体复合体结合的结构.
- 生物化学测试以评估在FACT存在或不存在的情况下的Chd1重塑活性.
- 对Chd1-核酶体相互作用的结构分析.
主要成果:
- 两个冷EM结构显示了Chd1与六体-核体复合体结合,在FACT的H2A/H2B二元恢复之前和之后.
- Chd1 独特地与该复合体相互作用,利用其ATPase 域将六体离核体转移.
- 在没有H2A/H2B二元体的情况下,Chd1的DNA结合域 (DBD) 与其ATPase域相对应,表明它处于抑制状态.
- H2A/H2B二元体的FACT介导的恢复触发了一种构造变化,它取代了DBD并激活了Chd1重塑.
结论:
- Chd1重塑活动是由内部H2A/H2B基因组二次体的存在调节的.
- 实际上,FACT充当了休斯伴侣来恢复二元体,从而刺激了Chd1.1.
- 这些发现揭示了Chd1和FACT如何合作维持染色质组织并促进RNAPII转录的机制.
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