基因组的修改调节了先驱转录因子的合作性
Kalyan K Sinha1, Silvija Bilokapic1, Yongming Du1
1Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature
|May 24, 2023
概括
像OCT4和SOX2这样的先驱转录因子合作获取压缩的DNA. 这项研究揭示了OCT4结合如何改变核体结构,使合作结合并促进细胞编程的染色体分解.
科学领域:
- 分子生物学
- 表观遗传学
- 结构生物学
背景情况:
- 开拓性转录因子 (PTF) 可以访问压缩的染色体.
- OCT4和SOX2之间的合作对于多能性和重编程至关重要.
- PTF功能和对染色质的合作机制尚未完全理解.
研究的目的:
- 阐明先驱转录因子OCT4功能和对染色体的合作的分子机制.
- 确定OCT4介导核细胞重塑和转录因子结合的结构基础.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定与核细胞结合的OCT4的结构.
- 生物化学测试以评估核细胞结构的变化和转录因子的结合.
- 基因相互作用和翻译后修改的分析.
主要成果:
- OCT4 的结合会诱导核细胞结构的变化和重置DNA,从而促进 OCT4 和 SOX2 的合作结合.
- OCT4的激活域与基因组H4的N端尾相互作用,促进染色体的分解.
- OCT4的DNA结合域与基因素H3的N端尾相互作用,H3K27的修饰影响了DNA定位和转录因子的合作性.
结论:
- OCT4积极重塑核体,使其自身和SOX2的结合成为可能,从而促进转录因子的合作.
- OCT4和基因组尾巴 (H3和H4) 之间的相互作用是染色体调节的关键.
- 通过像H3K27这样的基因组修饰,表观遗传场景可以调节OCT4活动以实现精确的细胞编程.
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