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转录抑制重复衍生转录本与衰老小鼠大脑中重复 DNA 元件的组蛋白低乙酰化相关。

Transcriptional repression of repeat-derived transcripts correlates with histone hypoacetylation at repetitive DNA elements in aged mice brain.

机构信息

Department of Biological Sciences, KAIST, Daejeon 305-701, South Korea.

出版信息

Exp Gerontol. 2011 Oct;46(10):811-8. doi: 10.1016/j.exger.2011.07.001. Epub 2011 Jul 18.

Abstract

In order to better characterize epigenetic alterations at repetitive DNA elements with aging, DNA methylation and histone marks at various repeat classes were investigated. Repetitive DNA elements were hypermethylated in the brains of old mice. Histone hypoacetylation and altered histone trimethylation at repetitive sequences were detected in brain tissues during aging. The expression of repeat-derived transcripts (RDTs) was then measured to explore any correlations with the observed epigenetic alterations. Large numbers of RDTs investigated were down-regulated along with age. Bisulfite sequencing revealed that CpG dinucleotide methylation patterns at the repeats of the RDT promoter region were mostly well maintained during aging. ChIP assay showed that histones were deacetylated at the promoter region of RDTs in aged mice brain. The observations indicate that the transcriptional repression of RDTs appears to be related to histone hypoacetylation, but not to DNA hypermethylation at repeat DNA elements in the brains of aged mice.

摘要

为了更好地描述与衰老相关的重复 DNA 元件的表观遗传改变,研究了各种重复类别的 DNA 甲基化和组蛋白标记。随着年龄的增长,老年小鼠大脑中的重复 DNA 元件出现过度甲基化。在衰老过程中,脑组织中检测到重复序列的组蛋白低乙酰化和组蛋白三甲基化改变。然后测量重复衍生转录物 (RDT) 的表达,以探索与观察到的表观遗传改变的任何相关性。大量研究的 RDT 随着年龄的增长而下调。亚硫酸氢盐测序显示,RDT 启动子区域重复序列的 CpG 二核苷酸甲基化模式在衰老过程中大多得到很好的维持。ChIP 检测表明,在老年小鼠大脑中,RDTs 的启动子区域的组蛋白被去乙酰化。这些观察结果表明,RDTs 的转录抑制似乎与组蛋白低乙酰化有关,而与老年小鼠大脑中重复 DNA 元件的 DNA 高甲基化无关。

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