循環器調節剤 CLOCK はヒストンアセチルトランスフェラーゼである
Masao Doi1, Jun Hirayama, Paolo Sassone-Corsi
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, B.P. 10142, 67404 Illkirch, Strasbourg, France.
Cell
|May 9, 2006
まとめ
昼間の時計の重要な部分であるCLOCKタンパク質は,ヒストンアセチルトランスファーゼ (HAT) 活性を持っています. このHAT機能は,日中リズムとクロック遺伝子発現の調節に不可欠であり,クロマチンの改造と細胞生理学の間のつながりを明らかにしています.
科学分野:
- クロノバイオロジーはクロノバイオロジーを用います.
- 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:
- シルカディアンリズム性は,時間固有の遺伝子転写を生成する分子機構によって制御されます.
- 昼間の時計におけるクロマチンの改造の機能は,ほとんど不明のままである.
研究 の 目的:
- シルカディアンリズム調節におけるCLOCKタンパク質の役割を調査する.
- CLOCKがクロマチンの改変に関連した酵素活性を持っているかどうかを判断する.
主な方法:
- CLOCKタンパク質のヒストンアセチルトランスファーゼ (HAT) 活性を評価した.
- CLOCKのHAT活動が,クロック変異細胞の昼夜リズムに与える影響を調べました.
- CLOCKとそのパートナーであるBMALとの相互作用を分析した1.
主要な成果:
- 本質的なヒストンアセチルトランスファーゼ (HAT) 活性を持つ新しいDNA結合タンパク質としてCLOCKを特定しました.
- BMAL1がCLOCK.のHAT活動を強化することを実証した.
- CLOCKのHAT活動は,日中リズムを回復し,変異細胞の時計遺伝子を活性化するために不可欠であることを示しました.
結論:
- CLOCKはDNAを結合するHATとして機能し,コア生理時時計のメカニズムにおけるクロマチンの改造を意味する.
- ヒストンアセチル化は,細胞生理学と昼夜リズムと直接関連しています.
- エピジェネティック・レギュレーションと生物学的タイミングの間の新しいつながりを明らかにした.
関連する概念動画
Histone 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,...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Histone 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,...
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...


