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学科主题: 基础医学
题名:
The Retinoblastoma Protein Selectively Represses E2F1 Targets via a TAAC DNA Element during Cellular Senescence
作者: Chen, Tianda; Xue, Lixiang; Niu, Jing; Ma, Liwei; Li, Na; Cao, Xiaoxiao; Li, Qian; Wang, Meng; Zhao, Wenting; Li, Guodong; Wang, Jiamu; Tong, Tanjun
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2012-10-26
DOI: 10.1074/jbc.M111.260679
卷: 287, 期:44, 页:37540-37551
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]: HUMAN FIBROBLASTS ; TUMOR-SUPPRESSOR ; HETEROCHROMATIN FORMATION ; REPLICATIVE SENESCENCE ; GENES ; CYCLE ; PROLIFERATION ; ACTIVATION ; P27(KIP1) ; MYB
英文摘要:

The retinoblastoma (Rb) protein mediates heterochromatin formation at the promoters of E2 transcription factor 1 (E2F1) target genes, such as proliferating cell nuclear antigen and cyclin A2 (CCNA2), and represses these genes during cellular senescence. However, the selectivity of Rb recruitment is still not well understood. Here, we demonstrate that a senescence-associated gene is a direct target of E2F1 and is also repressed by heterochromatin in senescent cells. In contrast, ARF and p27(KIP1), which are also E2F1 targets, are not repressed by Rb and heterochromatin formation. By comparing the promoter sequences of these genes, we found a novel TAAC element that is present in the cellular senescence-inhibited gene, proliferating cell nuclear antigen, and CCNA2 promoters but absent from the ARF and p27KIP1 promoters. This TAAC element associates with Rb and is required for Rb recruitment. We further determined that TAAC element-mediated Rb association requires the E2F1 binding site, but not E2F1 protein. These results provide a novel molecular mechanism for the different expression patterns of E2F1 targets and afford new mechanistic insight regarding the selectivity of Rb-mediated heterochromatin formation and gene repression during cellular senescence.

语种: 英语
所属项目编号: 2012CB911200 ; 2013CB530801 ; 30973146 ; 31000609 ; 31071206 ; 20090001120044
项目资助者: National Basic Research Programs of China ; National Natural Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China
WOS记录号: WOS:000310588500082
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55750
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:
Chen, Tianda,Xue, Lixiang,Niu, Jing,et al. The Retinoblastoma Protein Selectively Represses E2F1 Targets via a TAAC DNA Element during Cellular Senescence[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(44):37540-37551.
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