学科主题基础医学
FOXA1 mediates p16(INK4a) activation during cellular senescence
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
2013-03-20
DOI10.1038/emboj.2013.35
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
WOS记录号WOS:000316463600011
项目编号2013CB530801 ; 2012CB911203 ; 81170319
资助机构National Basic Research Programs of China ; National Natural Science Foundation of China
引用统计
被引频次:22[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/400002259/67634
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
作者单位Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Res Ctr Aging, Beijing 100191, Peoples R China
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GB/T 7714
Li, Qian,Zhang, Yu,Fu, Jingxuan,et al. FOXA1 mediates p16(INK4a) activation during cellular senescence[J]. EMBO JOURNAL,2013,32(6):858-873.
APA Li, Qian.,Zhang, Yu.,Fu, Jingxuan.,Han, Limin.,Xue, Lixiang.,...&Tong, Tanjun.(2013).FOXA1 mediates p16(INK4a) activation during cellular senescence.EMBO JOURNAL,32(6),858-873.
MLA Li, Qian,et al."FOXA1 mediates p16(INK4a) activation during cellular senescence".EMBO JOURNAL 32.6(2013):858-873.
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