对于DNA访问的bHLH转录因子和基因组之间的合作
Alicia K Michael1,2, Lisa Stoos1,2, Priya Crosby3
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nature
|July 5, 2023
概括
转录因子MYC-MAX和CLOCK-BMAL1与核细胞内的DNAE盒结合. 它们将DNA从基因质突移到结合部位,影响基因调节和昼夜节律.
科学领域:
- 分子生物学
- 表观遗传学
- 结构生物学
背景情况:
- 基本的螺旋环-螺旋环 (bHLH) 家族包括108个与DNA E-box (CANNTG) 结合的转录因子.
- 了解这些因素如何与染色体DNA相互作用对于解读基因调节至关重要.
研究的目的:
- 通过两种不同的bHLH蛋白:MYC-MAX和CLOCK-BMAL1来研究染色体E盒的参与.
- 阐明bHLH蛋白与核细胞DNA结合的结构机制.
主要方法:
- 使用工程和原生核细胞序列的结构研究.
- 蛋白质-DNA和蛋白质-基因素相互作用的分析.
主要成果:
- 无论是MYC-MAX还是CLOCK-BMAL1,都与核细胞进出处附近的E盒结合.
- 这些bHLH蛋白诱导DNA从基因组释放以获取.
- CLOCK- BMAL1与H2A- H2B酸性补丁相互作用,而MYC- MAX则与H2B和H3基因组相互作用.
- 核体E盒定位和bHLH二元化域决定了基因素接触和结合动态.
结论:
- bHLH转录因子采用不同的策略来访问和结合核体E盒.
- 对于bHLH蛋白结合亲和力和调节功能来说,基因组相互作用至关重要.
- 这些发现提供了对染色体中转录因子对基因表达的调节的见解.
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