通过基因素H3甲基化和酸化来调节HP1-染色蛋白结合
Wolfgang Fischle1, Boo Shan Tseng, Holger L Dormann
1Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA. fischlw@rockefeller.edu
Nature
|October 14, 2005
概括
希斯H3氨酸9甲基化招募异性染色素蛋白1 (HP1). 然而,M阶段的H3血清10酸化会排出HP1,揭示了一个新的表观遗传调节机制.
科学领域:
- 表观遗传学和分子生物学
- 细胞循环规则 细胞循环规则
- 染色体动力学 染色体动力学
背景情况:
- 基因组H3氨酸9三甲基化 (H3K9me3) 对于异性染色素蛋白1 (HP1) 结合和基因沉默至关重要.
- HP1蛋白对于染色质的包装和异染色质的形成至关重要.
- 了解细胞周期期间的HP1动态是理解基因调节的关键.
研究的目的:
- 为了研究HP1在M阶段从染色质释放的机制.
- 阐明基因组修饰在调节HP1解离中的作用.
- 确定在线粒分裂过程中参与HP1动态的关键因素.
主要方法:
- 染色体免疫沉 (ChIP) 评估HP1和基因组修饰水平.
- 细胞周期分析和线粒体染色体的准备.
- 抑制和消耗特定的激酶,如奥罗拉B.
主要成果:
- 尽管H3K9me3水平稳定,但HP1alpha, -beta和 -gamma在M阶段从染色质中释放出来.
- 在H3K9me3旁边的H3H3血清10酸化 (H3S10ph) 足以取代HP1.1.
- 抑制 Aurora B 激酶可以防止 HP1 解离,证实 H3S10ph 对于 HP1 释放的必要性.
结论:
- H3S10ph是一种关键的,短暂的修饰,它介于M阶段中HP1从染色质中排出的HP1.
- 稳定的H3K9me3和动态的H3S10ph之间的相互作用决定了HP1-染色体相互作用.
- 这种相邻的翻译后修改的组合读数代表了细胞周期依赖基因表达的新型调节机制.
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.
02:32Histone 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...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
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,...