单不和脂肪酸将H3K4me3修饰剂与C. elegans的寿命联系起来
Shuo Han1,2, Elizabeth A Schroeder1, Carlos G Silva-García3
1Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.
Nature
|April 6, 2017
概括
通过H3K4me3甲基转移酶缺乏修改染色体,通过增加脂肪积累,特别是单不和脂肪酸 (MUFA),延长虫的寿命. 饮食中的MUFA足以延长寿命,这表明长寿的机制得到了保护.
科学领域:
- 表观遗传学
- 代谢过程
- 老龄化研究
背景情况:
- 染色质状态和代谢过程是已知的寿命调节者.
- COMPASS染色体及其在素H3素4三甲基化 (H3K4me3) 中的作用影响了C. elegans* 的寿命.
- 关联H3K4me3修饰与寿命和潜在代谢参与的确切机制尚不清楚.
研究的目的:
- 研究H3K4me3修饰剂影响寿命的机制.
- 确定这种机制是否涉及代谢变化,特别是脂肪积累和组成.
- 探索单不和脂肪酸 (MUFA) 在H3K4me3中介寿命延长中的作用.
主要方法:
- 使用了H3K4me3甲基转移酶缺陷的C.elegans模型.
- 通过生物化学测试分析脂肪积累和脂肪酸组成的变化.
- 研究了生殖系和肠道组织的基因表达变化,重点是S6激酶和delta-9脂肪酸脱酶.
- 评估了饮食中的MUFA对寿命的影响.
主要成果:
- H3K4me3甲基转移酶缺乏导致脂肪积累增加,富含MUFA.
- 这种代谢转变与S6激酶和肠道delta- 9脂肪酸脱酸酶的激活等生殖目标的下调有关.
- 在缺陷虫中观察到的寿命延长中,MUFA积累是必不可少的.
- 饮食补充MUFA足以延长寿命.
结论:
- H3K4me3甲基转移酶缺陷通过重新编程脂肪代谢以增加MUFA,延长了C. elegans的寿命.
- 这种代谢转换的媒介是生殖线目标的下调和肠道脱酶的上调.
- MUFA是H3K4me3调节的长寿途中的一个关键组成部分.
- 研究结果表明,涉及MUFA的潜在治疗策略可以延长哺乳动物的寿命和健康期.
相关概念视频
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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
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Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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...
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,...