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学科主题: 基础医学
题名:
Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
作者: Zhou, Rui; Han, Limin; Li, Guodong; Tong, Tanjun
刊名: NUCLEIC ACIDS RESEARCH
发表日期: 2009-08-01
DOI: 10.1093/nar/gkp533
卷: 37, 期:15, 页:5183-5196
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: CELLULAR SENESCENCE ; TUMOR-SUPPRESSOR ; CHROMATIN STRUCTURE ; DNA METHYLATION ; GENE-EXPRESSION ; GROWTH-FACTOR ; SNF2 FAMILY ; HUMAN-CELLS ; IMMORTALIZATION ; TRANSCRIPTION
英文摘要:

Lymphoid specific helicase (Lsh) belongs to the family of SNF2/helicases. Disruption of Lsh leads to developmental growth retardation and premature aging in mice. However, the specific effect of Lsh on human cellular senescence remains unknown. Herein, we report that Lsh overexpression delays cell senescence by silencing p16(INK4a) in human fibroblasts. The patterns of p16(INK4a) and Lsh expression during cell senescence present the inverse correlation. We also find that Lsh requires histone deacetylase (HDAC) activity to repress p16(INK4a) and treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Lsh. Moreover, overexpression of Lsh is correlated with deacetylation of histone H3 at the p16 promoter, and TSA treatment in Lsh-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate an interaction between Lsh, histone deacetylase 1 (HDAC1) and HDAC2 in vivo. Furthermore, we demonstrate that Lsh interacts in vivo with the p16 promoter and recruits HDAC1. Our data suggest that Lsh represses endogenous p16(INK4a) expression by recruiting HDAC to establish a repressive chromatin structure at the p16(INK4a) promoter, which in turn delays cell senescence.

语种: 英语
所属项目编号: 2007CB507400 ; 30671064
项目资助者: National Basic Research Programs of China ; National Natural Science Foundation of China
WOS记录号: WOS:000270016400025
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65161
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, Res Ctr Aging, Dept Biochem & Mol Biol, Hlth Sci Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Zhou, Rui,Han, Limin,Li, Guodong,et al. Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts[J]. NUCLEIC ACIDS RESEARCH,2009,37(15):5183-5196.
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