通过DNA和基因组甲基化调节的核细胞相互作用蛋白
Till Bartke1, Michiel Vermeulen, Blerta Xhemalce
1The Gurdon Institute, Department of Pathology, Cambridge, UK.
Cell
|October 30, 2010
概括
研究人员确定了DNA和基因组甲基化之间的交叉声,揭示了像起源识别复合体这样的蛋白质如何与核细胞结合. 这项工作引入了一种用于研究色素修饰动态的新方法.
科学领域:
- 表观遗传学和染色体生物学
- 分子生物学分子生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 染色体功能是由DNA和基因组的修改调节的,这些基因组会招募特定的蛋白质.
- 了解不同类型的修饰之间的相互作用或"交叉声"对于破译基因调节至关重要.
研究的目的:
- 根据DNA和基因素甲基化模式,识别与核细胞相互作用的蛋白质.
- 在蛋白质招募中研究DNA甲基化和基因素甲基化之间的"交叉".
- 建立一种新的方法来分析染色体修饰相互作用的动态.
主要方法:
- 在亲和度测试中利用了DNA和基因组H3上甲基化的核细胞.
- 采用基于SILAC (细胞培养中氨基酸的稳定同位素标记) 的蛋白质组分析.
- 开发了SILAC核细胞相亲性净化 (SNAP) 技术,用于识别蛋白相互作用体.
主要成果:
- 鉴定了通过CpG,H3K4,H3K9和H3K27的甲基化调节核细胞结合的蛋白质.
- 发现原产地识别复合体 (ORC),包括LRWD1,作为一种甲基化敏感的交互因子,通过结合DNA和基因素甲基化来招募.
- 研究人员发现,一些基因组甲基结合蛋白,如Fbxl11/KDM2A,被DNA甲基化破坏.
结论:
- 建立了SNAP作为研究不同染色质修饰之间的相互作用的宝贵工具.
- 提供了关于DNA和基因组甲基化如何集体调节蛋白质与核细胞结合的见解.
- 通过结合表观遗传标记影响的特征性特定蛋白质结合"配置文件".
相关概念视频
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,...
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...
The 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...
The 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...
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...


