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学科主题: 基础医学
题名:
Transcriptional activation of the senescence regulator Lsh by E2F1
作者: 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
发表日期: 2011-04-01
DOI: 10.1016/j.mad.2011.03.004
卷: 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
所属项目编号: 2007CB507400 ; 30973146
项目资助者: National Basic Research Programs of China ; National Natural Science Foundation of China
WOS记录号: WOS:000291628000006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59894
Appears in Collections:基础医学院_北京大学衰老研究中心_期刊论文

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作者单位: Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China

Recommended Citation:
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.
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