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ホルモン誘発の転写性減圧におけるDNA脱メチル化
Mi-Sun Kim1, Takeshi Kondo, Ichiro Takada
1ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchisi, Saitama 332-0012, Japan.
Nature
|October 16, 2009
まとめ
遺伝子転写のホルモン調節には,ダイナミックなDNAメチル化と脱メチル化が含まれています. 副甲状腺ホルモンは,MBD4.4に依存するプロセスである活性DNA脱甲基化を誘導することによって,CYP27B1遺伝子を活性化します.
科学分野:
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- エピジェネティックの改変,特にヒストンの改変は,遺伝子調節に影響を与えます.
- 遺伝子の活性化における活性DNA脱メチル化のメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- 遺伝子転写のホルモン制御におけるDNAメチル化と脱メチル化の役割を調査する.
- ビタミンDと副甲状腺ホルモンがCYP27B1遺伝子を調節する分子メカニズムを解明する.
主な方法:
- 細胞のホルモン治療と,CYP27B1プロモーターにおけるDNAメチル化状態の分析.
- nVDRE結合タンパク質 (VDIR/TCF3) と関連したタンパク質複合体の生化学浄化.
- Mbd4ノックアウトマウスにおけるDNA脱メチル化と遺伝子転写の評価.
主要な成果:
- ビタミンDは,CYP27B1プロモーターのDNAメチル化を誘導し,転写を抑制する.
- 副甲状腺ホルモンは,CYP27B1プロモーターの活性DNA脱メチル化を誘導し,転写を活性化します.
- MBD4,DNMT1,DNMT3Bはメチル化/脱メチル化スイッチに関与し,MBD4のグリコシラーゼ活動は,副甲状腺ホルモン誘発の脱メチル化に不可欠である.
結論:
- DNAメチル化と脱メチル化スイッチングは,遺伝子転写のホルモン制御の重要なメカニズムです.
- MBD4によって媒介される活性DNA脱メチル化は,副甲状腺ホルモン誘発CYP27B1遺伝子活性化において重要な役割を果たします.
関連する概念動画
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Eukaryotic Transcription Inhibitors
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
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,...
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,...

