チャペロンRtt106によるH3K56-アセチルヒストンH3-H4の認識のための構造的基礎 Rtt106
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nature
|February 7, 2012
まとめ
ヒストンチャペロンRtt106は,H3-H4をN末端とPHドメインを通して結合し,DNA複製と修復のためにアセチル化H3K56acを認識します. この相互作用は,遺伝子サイレンシングとDNA損傷反応において極めて重要です.
科学分野:
- 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
- クロマチンのダイナミクス
背景:
- ヒストンの翻訳後の改変によって調節される染色体構造のダイナミクスは,DNAに関連するプロセスに影響を与えます.
- ヒストンH3ライシン56アセチル化 (H3K56ac) は,核細胞の組立と分解に不可欠です.
- ヒストンチャペロンRtt106はH3K56acの堆積を促進しますが,その結合メカニズムは不明です.
研究 の 目的:
- Rtt106がH3-H4複合体,特にH3K56ac.を認識し結合する分子メカニズムを解明する.
- DNA複製,修復,転写中の染色体調節におけるRtt106の役割を調査する.
主な方法:
- タンパク質とタンパク質の相互作用を研究するための生化学的測定法.
- Rtt106ドメインの構造分析.
- Saccharomyces cerevisiaeにおける機能的測定法について.
主要な成果:
- Rtt106は,アセチル化とは独立して,同位体化とH3-H4相互作用のためにそのN端領域を使用します.
- Rtt106のダブルプレックストリンホモロジー (PH) ドメインは,H3のK56を含む領域に結合し,H3K56ac.ac.に対する親和性が強化されています.
- Rtt106ジメルがH3-H4テトラメールにインターカレートし,PHドメインがH3K56acサイトを巻き込むモデル.
結論:
- Rtt106は,H3-H4の組み合わせ認識戦略を採用し,アセチル化依存および独立した相互作用を含む.
- Rtt106-H3-H4の相互作用は,遺伝子サイレンスを維持し,DNA損傷反応を促進するために不可欠です.
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...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:41Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
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...