学科主题基础医学
Transcriptional activation of the senescence regulator Lsh by E2F1
Niu, Jing; Chen, Tianda; Han, Limin; Wang, Pan; Li, Na; Tong, Tanjun
关键词Lsh E2F1 Transcriptional regulation Cellular senescence
刊名MECHANISMS OF AGEING AND DEVELOPMENT
2011-04-01
DOI10.1016/j.mad.2011.03.004
132期:4页:180-186
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Geriatrics & Gerontology
研究领域[WOS]Cell Biology ; Geriatrics & Gerontology
关键词[WOS]HUMAN-DIPLOID FIBROBLASTS ; CELL-PROLIFERATION ; TUMOR-SUPPRESSOR ; GENE-EXPRESSION ; FAMILY-MEMBER ; DNA-SYNTHESIS ; BINDING-SITE ; SNF2 FAMILY ; IN-VIVO ; APOPTOSIS
英文摘要

Lsh, a protein related to the SNF2 family of chromatin-remodeling ATPases, is a major epigenetic regulator that is essential for DNA methylation and histone acetylation at repetitive elements. Lsh represses endogenous p16(INK4a) expression by recruiting HDAC to the p(16IN4Ka) promoter, which in turn delays cell senescence. However, the molecular mechanisms that govern loss of Lsh expression during cellular senescence have yet to be elucidated. Here we investigate the transcriptional regulation of the human Lsh promoter. We find that the minimal Lsh promoter is located between positions -216 and -119 relative to the transcription start site, and contains two putative E2F binding sites. Ectopic E2F1 increases expression of Lsh at both transcriptional and translational levels. E2F1 physically interacts with the Lsh promoter by binding to each of the two putative binding sites and transactivates the Lsh promoter. E2F1 also induces Lsh protein expression and transactivates the Lsh promoter in 2BS cells. At the same time, E2F1-induced Lsh promoter activity is reduced in senescent cells compared to young cells. These results indicate that E2F1 plays a crucial role in transcriptional control of the human Lsh gene and the decrease of Lsh expression in senescent cells is related to the repression of E2F1. Published by Elsevier Ireland Ltd.

语种英语
WOS记录号WOS:000291628000006
项目编号2007CB507400 ; 30973146
资助机构National Basic Research Programs of China ; National Natural Science Foundation of China
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59894
专题北京大学基础医学院_北京大学衰老研究中心
北京大学基础医学院
北京大学精神卫生研究所_精神科
作者单位Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
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GB/T 7714
Niu, Jing,Chen, Tianda,Han, Limin,et al. Transcriptional activation of the senescence regulator Lsh by E2F1[J]. MECHANISMS OF AGEING AND DEVELOPMENT,2011,132(4):180-186.
APA Niu, Jing,Chen, Tianda,Han, Limin,Wang, Pan,Li, Na,&Tong, Tanjun.(2011).Transcriptional activation of the senescence regulator Lsh by E2F1.MECHANISMS OF AGEING AND DEVELOPMENT,132(4),180-186.
MLA Niu, Jing,et al."Transcriptional activation of the senescence regulator Lsh by E2F1".MECHANISMS OF AGEING AND DEVELOPMENT 132.4(2011):180-186.
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