リズムヒストンのアセチル化は,哺乳類の昼夜時計における転写の基礎となっている
Jean-Pierre Etchegaray1, Choogon Lee, Paul A Wade
1Department of Neurobiology, University of Massachusetts Medical School, LRB-728, 364 Plantation Street, Worcester, Massachusetts 01605, USA.
Nature
|December 17, 2002
まとめ
クリプトクロメスは,H3アセチル化リズムを調節することによって,マウス肝臓の昼夜時計の転写を阻害する. このp300とヒストンのアセチル化を含む表遺伝的メカニズムは,コアクロック遺伝子発現のタイミングを精製します.
科学分野:
- クロノバイオロジー クロノバイオロジー
- 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:
- マウスの昼間時計は,クロック,Bmal1,Period (Per),Cry (Cry) の遺伝子を含む転写フィードバックループに依存しています.
- クリプトクロームはDNA結合に影響を与えることなく,クロック/Bmal1の転写を阻害する.
研究 の 目的:
- ネズミの肝臓の昼間時計のメカニズムにおけるH3ヒストンアセチル化の役割を調査する.
- Cryptochromesが転写阻害のためにH3アセチル化を標的とするかどうかを決定する.
主な方法:
- 核時計遺伝子プロモーターにおけるH3アセチル化とRNAポリメラーゼII結合リズムの分析.
- ヒストンアセチルトランスフェラーゼp300とClockのインビボ共同降水.
- Cryptochromeがp300媒介トランスクリプションに及ぼす影響の評価.
主要な成果:
- H3アセチル化とRNAポリメラーゼII結合における昼夜リズムがPer1,Per2,Cry1プロモーターで観察され,mRNAリズムと同期された.
- ヒストンアセチルトランスフェラーゼp300は,時間に依存した方法で時計で沈殿することが判明しました.
- クリプトクロームは,p300誘発のクロック/Bmal1媒介の転写を抑制することが示されました.
結論:
- H3ヒストンのアセチル化リズムは,マウスの肝臓の昼間時計の転写調節に伴います.
- クリプトクロームは,H3アセチレーションをターゲットにすることで,核時計遺伝子転写を阻害する.
- Rev-ErbalphaとClock/Bmal1の連携した作用は,Cry1 mRNAのリズムタイミングを調節し,新しい昼夜周期制御メカニズムを明らかにします.
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,...
02:19Circadian 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,...
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...
02:38Heterochromatin
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...
02:32Histone 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,...
02:19Circadian 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,...