通过植物甲基转移酶DRM2进行上下文依赖的非CG CHH甲基化中的DNA构造动态
Jianbin Chen1, Jiuwei Lu1, Jie Liu2
1Department of Biochemistry, University of California, Riverside, California, USA.
The Journal of biological chemistry
|November 5, 2023
概括
植物DNA甲基转移酶DRM2更喜欢用于CHH甲基化的特定DNA序列,受侧边核酸和温度依赖的DNA灵活性的影响,揭示了表观遗传调节的机制.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 植物科学 植物科学
背景情况:
- 基因甲基化是调节植物基因表达和基因组稳定的关键表观遗传机制.
- 非CGDNA甲基化,特别是CHH甲基化,在植物中普遍存在,并且取决于环境,受侧面序列的影响.
- 影响非CG甲基化的DNA序列, conformation 和动态的精确机制在很大程度上是未知的.
研究的目的:
- 在结构和生物化学上描述DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) 的基质偏好.
- 阐明侧边核酸序列和DNA动态如何影响DRM2-介导的CHH甲基化.
- 了解温度在调节DRM2的基质偏好和甲基化活性中的作用.
主要方法:
- 使用X射线结晶学对DRM2甲基转移酶 (MTase) 域进行结构性表征.
- 生物化学试验以确定DRM2对各种CHH基因的内在基质偏好.
- 对具有不同DNA复合体的DRM2-DNA复合体进行比较结构分析,包括具有灵活TPA步骤的复合体.
主要成果:
- DRM2 MTase域对CWW (W=A或T) CHH动机表现出明显的基质偏好,与它们在植物中的丰度相关.
- 晶体结构揭示了侧边核酸组成,特别是 +1/+2 位点的灵活 TpA 阶段,如何影响 DRM2 结合和甲基化.
- 在TpA阶段的DNA灵活性导致了替代性构造,改变了DRM2相互作用,并导致基质偏好的温度依赖转移.
结论:
- DRM2的上下文依赖的CHH甲基化是由它对特定的侧面序列和DNA构造动态的内在偏好决定的.
- DNA灵活性,温度和DRM2结构之间的相互作用为环境影响的表观遗传调节提供了机制基础.
- 这项研究提供了对植物非CG DNA甲基化建立和维护背后的分子机制的关键见解.
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