ヒストンH3のプロリンイソメリゼーションは,ライシンメチレーションと遺伝子発現を調節する
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
まとめ
Fpr4によるプロリンイソメリゼーションはヒストンメチレーションを調節する. この新しい非共性ヒストンの改変は,H3K36.3のSet2メチル化に対抗することによって,遺伝子転写を制御する.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
背景:
- プロリンシストランスイソメリゼーションは,細胞信号伝達経路における重要な規制メカニズムです.
- ヒストンの改変は,遺伝子発現とクロマチンの構造を調節する上で重要な役割を果たします.
研究 の 目的:
- ヒストンの改変に関与するプロリンイソメラーゼを特定し,特徴づけること.
- ヒストンのメチル化と遺伝子転写の調節におけるプロリンイソメリゼーションの役割を調査する.
主な方法:
- プロリンイソメリゼーションとヒストンメチル化を研究するためのインビトロ酵素分析.
- Fpr4.4によるヒストン尾結合の生化学分析.
- ヒストンのメチル化と遺伝子発現にFpr4の活性が及ぼす影響を評価するために,Saccharomyces cerevisiaeの体内実験を行いました.
主要な成果:
- プロリンイソメラーゼであるFpr4はヒストンH3とH4の尾と結合し,H3プロリン残基P30とP38.3のイソメリゼーションを触媒化する.
- H3 P38のイソメリゼーションはK36メチル化に不可欠であり,Fpr4媒介のイソメリゼーションはSet2依存のH3 K36メチル化をin vitroで抑制する.
- in vivoでFpr4の触媒活性を失うと,H3K36のメチル化が増加し,転写運動が変化する.
結論:
- プロリンイソメリゼーションは,転写に影響を与える新しい非共性ヒストンの改変として作用します.
- Fpr4媒介のプロリンイソメリゼーションは,Set2によるH3K36メチル化に対抗し,これらの規制メカニズム間のクロストークを示しています.
- Fpr4によって調節されるH3 P38の構成状態は,Set2媒介のH3K36メチル化およびその後の遺伝子調節に不可欠である.
関連する概念動画
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...