激素诱导的转录性脱压缩中的DNA脱甲基化
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
概括
基因转录的荷尔蒙调节涉及动态DNA甲基化和脱甲基化. 甲状腺激素通过诱导活性DNA脱甲基化来激活CYP27B1基因,这种过程取决于MBD4.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 表观遗传修饰,特别是基因组变化,影响基因调节.
- 在基因激活中活性DNA脱甲基化的机制仍然不完全理解.
研究的目的:
- 研究DNA甲基化和脱甲基化在激素控制基因转录中的作用.
- 阐明维生素D和副甲状腺激素对CYP27B1基因的调节背后的分子机制.
主要方法:
- 细胞的荷尔蒙治疗和DNA甲基化状态在CYP27B1促进者的分析.
- 生物化学净化与nVDRE结合蛋白 (VDIR/TCF3) 相关的蛋白质复合体.
- 在Mbd4淘汰赛小鼠中评估DNA脱甲基和基因转录.
主要成果:
- 维生素D在CYP27B1促进体中诱导DNA甲基化,抑制转录.
- 副甲状腺激素诱导CYP27B1促进体的活性DNA脱甲基化,激活转录.
- MBD4,DNMT1和DNMT3B都参与甲基化/脱甲基化开关;MBD4的糖酶活性对于甲状腺激素诱导的脱甲基化至关重要.
结论:
- 基因甲基化和脱甲基化切换是激素控制基因转录的关键机制.
- 由MBD4介导的活性DNA脱甲基化在甲状腺激素诱导的CYP27B1基因激活中起着关键作用.
相关概念视频
01:37Epigenetic 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...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
01:52Eukaryotic 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...
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,...