在Serine 31中H3.3的酸化作为转录的核细胞体动态的开关
Jingzhe Ma1, Junran Zhang1, Xue Xiao2
1Department of Immunology, School of Basic Medical Sciences, Laboratory for Clinical Medicine, Capital Medical University, Beijing 100069, China.
Nucleic acids research
|September 18, 2025
概括
基因组变异H3.3保持了核细胞完整性,并招募了FACT复合体. 在Serine 31 (H3.3S31ph) 的酸化将H3.3-核糖体切换到动态状态,调节巨细胞中的基因转录.
科学领域:
- 表观遗传学和分子生物学
- 染色体动力学 染色体动力学
- 基因规则 基因规则
背景情况:
- 基因组变异H3.3对于基因转录,基因组稳定性和线粒分裂至关重要.
- 确切的机制,H3.3影响核细胞稳定性和动力学并没有完全理解.
- 了解H3.3的作用是解读基因调节和细胞过程的关键.
研究的目的:
- 研究H3.3的结合如何影响核细胞稳定性和动态.
- 通过H3.3.3阐明FACT复合体招聘的作用.
- 确定H3.3酸化在Serine 31 (H3.3S31ph) 对核细胞功能和转录调节的影响.
主要方法:
- 在体外核细胞稳定性测试.
- 对FACT复合体与含有H3.3的核细胞结合的分析.
- 对H3.3沉积和H3.3S31ph的全基因组分析.
- 巨细胞刺激测试用于评估转录反应.
主要成果:
- 添加H3.3可以增强核细胞的完整性,但不会显著改变稳定性.
- H3.3比正规的H3更有效地招募FACT复合体,抵消FACT破坏稳定的作用.
- H3.3S31ph逆转了FACT结合诱导的稳定,调节了核酶体动力学.
- 全基因组数据显示,H3.3和H3.3S31ph动态调节核酶体状态和巨细胞中的FACT结合.
结论:
- H3.3在维持核细胞完整性和促进FACT招募方面发挥着关键作用.
- H3.3S31ph 作为一个分子开关,将H3.3-核酶从稳定状态转换为动态状态.
- 这种动态调节对于响应刺激的快速转录激活至关重要,影响巨细胞的免疫反应.
更多相关视频
11:02Complete Workflow for Analysis of Histone Post-translational Modifications Using Bottom-up Mass Spectrometry: From Histone Extraction to Data Analysis
Published on: May 17, 2016
30.4K
09:26Reconstitution of Nucleosomes with Differentially Isotope-labeled Sister Histones
Published on: March 26, 2017
11.5K
相关概念视频
02:32Histone 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
02:32Histone Modification
4.4K
4.4K
01:12The 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
02:10The 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
02:25Spreading 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
01:02Phosphorylation
53.6K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
53.6K