DNAとヒストンのメチル化によって調節される核細胞相互作用タンパク質です
Till Bartke1, Michiel Vermeulen, Blerta Xhemalce
1The Gurdon Institute, Department of Pathology, Cambridge, UK.
Cell
|October 30, 2010
まとめ
研究者らはDNAとヒストンのメチル化との交差を特定し,起源認識複合体のようなタンパク質が核細胞にどのように結合するかを明らかにした. この研究は,染色体変異のダイナミクスを研究するための新しい方法を導入しています.
科学分野:
- エピジェネティクスとクロマチン生物学
- 分子生物学は分子生物学である.
- プロテオミクス プロテオミクスは,プロテオミクスの
背景:
- 染色体の機能は,DNAとヒストンの改変によって調節され,それらは特定のタンパク質を勧誘する.
- 異なる種類の改変の間の相互作用,または"クロスストーク"を理解することは,遺伝子調節を解読する上で極めて重要です.
研究 の 目的:
- DNAとヒストンのメチル化パターンを基に核細胞と相互作用するタンパク質を識別する.
- タンパク質の採用におけるDNAメチル化とヒストンのメチル化との"交差"を調査する.
- 染色体改変相互作用の動態を分析するための新しい方法の確立.
主な方法:
- アフィニティアッセイでDNAとヒストンH3にメチル化された核細胞を用いた.
- SILAC (Stable Isotope Labeling by Amino acids in Cell culture) ベースのプロテオミク解析を用いた. 細胞培養におけるアミノ酸による安定同位体ラベル付け) によるプロテオミク分析を用いた.
- タンパク質インタラクタを特定するために,開発したSILAC核細胞親和性浄化 (SNAP).
主要な成果:
- 核細胞結合がCpG,H3K4,H3K9,H3K27のメチル化によって調節されるタンパク質を特定した.
- LRWD1を含む起源認識複合体 (ORC) を,DNAとヒストンの結合メチル化により採用されたメチル化敏感相互作用体として発見した.
- Fbxl11/KDM2Aのようなヒストンのメチル結合タンパク質は,DNAメチル化によって破壊される.
結論:
- SNAPは,異なるクロマチンの改変の相互作用を研究するための貴重なツールとして確立されました.
- DNAとヒストンのメチル化が集団的に核細胞へのタンパク質結合を調節する方法についての洞察を提供した.
- 結合された表遺伝的マークによって影響された特定のタンパク質結合"プロファイル"を特徴づける.
関連する概念動画
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,...
02:32Histone 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...
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...
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...
02:54Nucleosome 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...