G34R癌症突变改变了基因组H3.3尾巴的结构组合和动态
Harrison A Fuchs1, Yunhui Peng2,3, Shine Ayyapan1
1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States.
Nucleic acids research
|January 14, 2026
概括
基质瘤中像G34R这样的希斯H3.3突变通过增加H3尾巴DNA结合和减少动力学来改变核细胞结构. 这些变化影响了与CHD4.4等蛋白质的相互作用.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 基因组变异H3.3中的突变与儿科和成人质瘤和骨髓瘤有关.
- 众所周知,H3.3 N-终端尾部的G34R突变会破坏表观基因组通路,但它对核细胞结构的直接影响尚不清楚.
研究的目的:
- 调查G34R癌症突变和相邻的G33R突变对核细胞结构动态的影响.
- 确定这些H3突变如何影响H3尾巴与核细胞DNA的相互作用.
主要方法:
- 核磁共振 (NMR) 光谱学 核磁共振 (NMR) 光谱学
- 分子动力学 (MD) 模拟
- 在核子组的背景下分析H3尾部构造和DNA相互作用.
主要成果:
- 两种G34R和G33R突变都增强了H3尾巴与DNA的关联.
- 这些突变会减少突变部位周围的构造动态,并改变尾巴的整体构造.
- 重定位的H3尾部促进尾部内相互作用,并影响CHD4植物宿主群指的结合.
结论:
- H3.3突变通过修改H3尾部动力学和DNA相互作用,直接改变核细胞结构.
- 这些结构变化具有功能性后果,影响调节蛋白与核细胞的结合.
相关概念视频
Histone Variants at the Centromere
4.9K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.9K
Histone Modification
15.9K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
15.9K
Histone Modification
4.4K
4.4K
Spreading of Chromatin Modifications
9.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
9.3K
The Nucleosome Core Particle
2.1K
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
2.1K
The Nucleosome Core Particle
14.1K
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
14.1K


