JMJD2ファミリーメンバーによるヒストンの脱メチル化に関する構造的洞察
Zhongzhou Chen1, Jianye Zang, Johnathan Whetstine
1Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Cell
|May 9, 2006
まとめ
研究者らは,JMJD2Aヒストン脱メチラーゼコアドメインの構造を決定した. この構造的洞察は,JMJD2ヒストンデメチラゼが基板を選択する方法の分子モデルを提供します.
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:
- ヒストンの翻訳後の改変は,クロマチンの構造と遺伝子発現の調節に不可欠です.
- ヒストンデメチラーゼは,新しいタイプの転写因子で,ヒストンライシン残基からメチル群を除去し,遺伝子転写に影響を与えます.
- JmjCドメインを含むタンパク質はヒストン脱甲基化として関与しており,JMJD2AはH3-K9me3およびH3-K36me3.3に特異性があると特定されています.
研究 の 目的:
- JMJD2Aヒストン脱メチラゼの活性性の構造的基礎を解明する.
- JMJD2ファミリーにおける基板選択の基礎となる分子メカニズムを理解する.
主な方法:
- X線結晶学を用いて,JMJD2A触媒核ドメインの構造を決定した.
- 構造はFe2+の存在下でアルファ-ケトグルタレートとそれなしで得られた.
- サイト指向型変異性およびデメチラゼ活性アッセイが実施されました.
主要な成果:
- JmjN,JmjC,C端末ドメイン,および亜鉛指モチーフを含むJMJD2A触媒核ドメインの結晶構造が決定されました.
- 潜在的基板結合ポケットを形成するユニークな構造要素が特定されました.
- JMJD2ヒストンデメチラゼファミリーによる基板選択の分子モデルが,ミュータゲネシスと活性データに基づいて提案されました.
結論:
- 決定された構造は,JMJD2A.の触媒機構に関する重要な洞察を提供します.
- この発見は,表遺伝的調節におけるヒストン脱メチラーゼの機能のより深い理解を容易にする.
- 提案されたモデルは,JMJD2ヒストンデメチラゼファミリー内の基板特異性を理解するのに役立ちます.
関連する概念動画
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...
02:30Histone 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...
02:32Histone 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...