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学科主题: 基础医学
题名:
FOXA1 mediates p16(INK4a) activation during cellular senescence
作者: Li, Qian; Zhang, Yu; Fu, Jingxuan; Han, Limin; Xue, Lixiang; Lv, Cuicui; Wang, Pan; Li, Guodong; Tong, Tanjun
关键词: FOXA1 ; p16(INK4a) ; polycomb complex ; senescence
刊名: EMBO JOURNAL
发表日期: 2013-03-20
DOI: 10.1038/emboj.2013.35
卷: 32, 期:6, 页:858-873
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: TRANSCRIPTION FACTORS ; REPLICATIVE SENESCENCE ; HUMAN FIBROBLASTS ; IN-VIVO ; GLUCOSE-HOMEOSTASIS ; GENE-EXPRESSION ; INK4A-ARF LOCUS ; TARGET GENES ; STEM-CELLS ; POLYCOMB
英文摘要:

Mechanisms governing the transcription of p16(INK4a), one of the master regulators of cellular senescence, have been extensively studied. However, little is known about chromatin dynamics taking place at its promoter and distal enhancer. Here, we report that Forkhead box A1 protein (FOXA1) is significantly upregulated in both replicative and oncogene-induced senescence, and in turn activates transcription of p16(INK4a) through multiple mechanisms. In addition to acting as a classic sequence-specific transcriptional activator, FOXA1 binding leads to a decrease in nucleosome density at the p16(INK4a) promoter in senescent fibroblasts. Moreover, FOXA1, itself a direct target of Polycomb-mediated repression, antagonizes Polycomb function at the p16(INK4a) locus. Finally, a systematic survey of putative FOXA1 binding sites in the p16(INK4a) genomic region revealed an similar to 150 kb distal element that could loop back to the promoter and potentiate p16(INK4a) expression. Overall, our findings establish several mechanisms by which FOXA1 controls p16(INK4a) expression during cellular senescence. The EMBO Journal (2013) 32, 858-873. doi:10.1038/emboj.2013.35; Published online 26 February 2013

语种: 英语
所属项目编号: 2013CB530801 ; 2012CB911203 ; 81170319
项目资助者: National Basic Research Programs of China ; National Natural Science Foundation of China
WOS记录号: WOS:000316463600011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67634
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, Dept Biochem & Mol Biol, Res Ctr Aging, Beijing 100191, Peoples R China

Recommended Citation:
Li, Qian,Zhang, Yu,Fu, Jingxuan,et al. FOXA1 mediates p16(INK4a) activation during cellular senescence[J]. EMBO JOURNAL,2013,32(6):858-873.
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