节律性素乙化是哺乳动物昼夜钟中转录的基础
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
概括
加密染色体通过调节H3乙化节奏来抑制小鼠肝脏昼夜时钟的转录. 这种表观遗传机制涉及p300和基因素乙化,改进了核心时钟基因表达的时间.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 鼠标的昼夜时钟依赖于涉及时钟,Bmal1,周期 (Per) 和加密色 (Cry) 基因的转录反循环.
- 加密染色体抑制了Clock/Bmal1的转录,但没有影响DNA结合.
研究的目的:
- 为了研究H3素乙化在小鼠肝脏昼夜时钟机制中的作用.
- 为了确定Cryptochromes是否针对H3乙化进行转录抑制.
主要方法:
- 在核心时钟基因促进者中分析H3乙化和RNA聚合酶II结合节奏.
- 在体内与Histone乙转移酶p300与Clock的共同沉.
- 对Cryptochrome对p300介导转录的影响的评估.
主要成果:
- 在Per1,Per2和Cry1促进器中观察到H3乙化和RNA聚合酶II结合的昼夜节律,与mRNA节律同步.
- 发现基酸转移酶p300以时间依赖的方式与时钟沉.
- 证实加密染色体可以抑制p300诱导的时钟/Bmal1介导的转录.
结论:
- 在小鼠肝脏的昼夜时钟中,H3基因素乙化节奏伴随着转录调节.
- 加密染色体通过向H3乙化来抑制核心时钟基因转录.
- Rev-Erbalpha和Clock/Bmal1的协调作用调节Cry1mRNA节律的时间,揭示了一个新的昼夜节律控制机制.
相关概念视频
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,...