MMSET调节了基因素H4K20甲基化和53BP1在DNA损伤部位的积累
Huadong Pei1, Lindsey Zhang, Kuntian Luo
1Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nature
|February 5, 2011
概括
通过局部H4K20甲基化促进p53结合蛋白1 (53BP1) 招募到DNA双链断裂 (DSB),这是由MMSET介导的过程. 这一途径对于DNA损伤反应至关重要.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 对DNA损伤的反应反应
背景情况:
- 53结合蛋白1 (53BP1) 对于DNA损伤反应至关重要.
- 基因组H4 lysine 20二甲基化 (H4K20me2) 对53BP1招募到双链断裂 (DSB) 的过程至关重要.
- 尽管H4K20me2水平稳定,但53BP1对DSB的精确向机制仍然不清楚.
研究的目的:
- 为了阐明53BP1针对DSB的机制.
- 调查H4K20甲基化在53BP1招募中的作用.
- 确定在DSB中负责局部H4K20甲基化的因素.
主要方法:
- 在哺乳动物细胞中诱导DSB.
- 在DSB中分析H4K20甲基化水平.
- 使用遗传方法降低基因组甲基转移酶MMSET的下调.
- 在MMSET招募中研究γH2AX-MDC1通路.
主要成果:
- 在DSB中,H4K20甲基化局部增加.
- 组织素甲基转移酶MMSET在DSB中调解H4K20甲基化.
- 低调 MMSET 降低了 H4K20 甲基化和 53BP1 在 DSB 的积累.
- 对DSB的MMSET招募取决于γH2AX-MDC1通路.
结论:
- 一个涉及γH2AX-MDC1-MMSET的新途径调节了DSB中的H4K20甲基化.
- 这种局部化的H4K20甲基化促进了53BP1的招募.
- 这些发现为调节DNA损伤反应途径提供了新的见解.
相关概念视频
Spreading of Chromatin Modifications
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 is an enzyme that can...
Writers
The writer is an enzyme that can...
Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...


