质素H3的林异构化调节了氨酸甲基化和基因表达
Christopher J Nelson1, Helena Santos-Rosa, Tony Kouzarides
1Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK.
Cell
|September 9, 2006
概括
通过Fpr4进行的林异构化调节了组织素甲基化. 这种新型的非对应性基因素修饰通过对抗H3K36.3的Set2甲基化来控制基因转录.
科学领域:
- 生物化学 生物化学
- 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.
背景情况:
- 氨酸的 cis-trans 异构化是细胞信号通路中的关键调节机制.
- 基因组蛋白修饰在调节基因表达和染色质结构方面起着至关重要的作用.
研究的目的:
- 为了识别和描述参与基因素修饰的林异构酶.
- 调查林异构化在调节基因素甲基化和基因转录中的作用.
主要方法:
- 在体外的酶分析来研究林异构化和基因素甲基化.
- 通过Fpr4.4对希斯尾结合的生物化学分析.
- 在Saccharomyces cerevisiae中的体内实验,以评估Fpr4活性对基因素甲基化和基因表达的影响.
主要成果:
- 一种普罗林异构酶Fpr4与基因素H3和H4尾部结合,并催化H3普罗林残基P30和P38.8的异构化.
- 对于K36甲基化,H3 P38的异构化是必不可少的,而Fpr4介导的异构化在体外抑制了Set2依赖的H3 K36甲基化.
- 活体内Fpr4催化活性的丧失导致H3K36甲基化增加和转录动力学变化.
结论:
- 林异构化作为一种影响转录的新型非对应性基因素修饰作用.
- 通过Fpr4介导的普林异构化对抗了Set2的H3K36甲基化,表明了这些调节机制之间的交叉声.
- 由Fpr4调节的H3 P38的构造状态对于Set2介导的H3K36甲基化和随后的基因调节至关重要.
相关概念视频
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:10The Nucleosome Core Particle
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...
02:32Histone 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,...
02:25Spreading 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...
02:32Histone 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,...
01:12The Nucleosome Core Particle
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...