関連する実験動画
Updated: Jul 14, 2026
09:47
Analysis of Histone Antibody Specificity with Peptide Microarrays
Published on: August 1, 2017
ヒストン脱メチラーゼJMJD2Aの結晶構造は,基板特異性の基礎を明らかにする
Stanley S Ng1, Kathryn L Kavanagh, Michael A McDonough
1Structural Genomics Consortium, Botnar Research Center, University of Oxford, Oxford OX3 7LD, UK.
Nature
|June 26, 2007
まとめ
研究者らは,JMJD2A酵素がヒストンタンパク質の異なるメチル化状態を区別する方法を明らかにした. この発見は,表遺伝的調節を理解し,新しい薬の開発に鍵となる.
科学分野:
- エピジェネティクス エピジェネティクス
- クロマチン生物学 クロマチン生物学
- 分子生物学は分子生物学である.
背景:
- メチル化を含む翻訳後のヒストンの改変は,表遺伝的調節に極めて重要です.
- リシル脱メチラゼはメチル基を除去し,永久的な表遺伝子マークとしてのメチル化という見方に異議を唱える.
- デメチラーゼの選択性を理解することは,生物学的プロセスにおけるそれらの役割を解読するために不可欠です.
研究 の 目的:
- ヒトのJMJD2A (2Aを含むジュモンジドメイン) が特定のヒストンメチル化状態 (H3K9me3/me2およびH3K36me3/me2) に対する選択性を達成する分子メカニズムを解明する.
- JMJD2Aがメチル化状態を区別し,特にH3K9.9の特定の配列を認識する方法を理解する.
主な方法:
- JMJD2A阻害剤複合体のX線結晶学により,様々なメチル化ヒストンH3ペプチド (H3K9me3/me2/me1およびH3K36me3) と結合する.
- JMJD2A活性部位における基板結合の構造分析.
主要な成果:
- 構造的な洞察は,基板が明確な曲げられた形状を採用するリシル結合ポケットを明らかにします.
- Zn結合部位は,基質の認識と結合に役割を果たします.
- 提案されたメカニズムは,フェリル中間体に対するメチル群の指向に基づいて,メチル化状態の選択性を説明する.
結論:
- JMJD2Aは,異なるメチル化状態と配列の識別メカニズムを示しています.
- これらの発見は,薬物の発見のための化学的ツールの開発のための基盤を提供します.
- この研究は,逆転性ヒストンメチル化とそのクロマチンの生物学における役割の理解を前進させる.
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,...
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...
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
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...