Identification and Characterization of Bmi-1-responding Element within   the Human p16 Promoter

doi:10.1074/jbc.M110.133686

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	Identification and Characterization of Bmi-1-responding Element within the Human p16 Promoter
	Meng, Sha ; Luo, Min ; Sun, He ; Yu, Xin ; Shen, Meili ; Zhang, Quancang ; Zhou, Rudan ; Ju, Xiaofang ; Tao, Wei ; Liu, Di ; Deng, Hongkui ; Lu, Zhigang
刊名	journal of biological chemistry
	2010
关键词	CELL SELF-RENEWAL HEMATOPOIETIC STEM-CELLS BMI-1 EXPRESSION P-GLYCOPROTEIN NEUROBLASTOMA-CELLS TELOMERASE ACTIVITY H2A UBIQUITYLATION TUMOR-SUPPRESSOR EPITHELIAL-CELLS INK4A/ARF LOCUS
DOI	10.1074/jbc.M110.133686
英文摘要	Bmi-1, the first functionally identified polycomb gene family member, plays critical roles in cell cycle regulation, cell immortalization, and cell senescence. Bmi-1 is involved in the development and progression of carcinomas and is a potent target for cancer therapy. One important pathway regulated by Bmi-1 is that involving two cyclin-dependent kinase inhibitors, p16(Ink4a) and p19(Arf), as Bmi-1 represses the INK4a locus on which they are encoded. A close correlation between the up-regulation of Bmi-1 and down-regulation of p16 has been demonstrated in various tumors; however, how Bmi-1 regulates p16 expression is not clear. In this study, we revealed that Bmi-1 regulates the expression of p16 by binding directly to the Bmi-1-responding element (BRE) within the p16 promoter. The BRE resided at bp -821 to -732 upstream of the p16 ATG codon. BRE alone was sufficient to allow Bmi-1-mediated regulation of the CMV promoter. Bmi-1 typically functions by forming a complex with Ring2; however, regulation of p16 was independent of Ring2. Chromatin immunoprecipitation sequencing of Bmi-1-precipitated chromatin DNA revealed that 1536 genes were targeted by Bmi-1, including genes involved in tissue-specific differentiation, cell cycle, and apoptosis. By analyzing the binding sequences of these genes, we found two highly conserved Bmi-1-binding motifs, which were required for Bmi-1-mediated p16 promoter regulation. Taken together, our results revealed the molecular mechanism of Bmi-1-mediated regulation of the p16 gene, thus providing further insights into the functions of Bmi-1 as well as a sensitive high-throughput platform with which to screen Bmi-1-targeted small molecules for cancer therapy.; Biochemistry & Molecular Biology; SCI(E); PubMed; 16; ARTICLE; 43; 33219-33229; 285
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/344195]
专题	生命科学学院
推荐引用方式 GB/T 7714	Meng, Sha,Luo, Min,Sun, He,et al. Identification and Characterization of Bmi-1-responding Element within the Human p16 Promoter[J]. journal of biological chemistry,2010.
APA	Meng, Sha.,Luo, Min.,Sun, He.,Yu, Xin.,Shen, Meili.,...&Lu, Zhigang.(2010).Identification and Characterization of Bmi-1-responding Element within the Human p16 Promoter.journal of biological chemistry.
MLA	Meng, Sha,et al."Identification and Characterization of Bmi-1-responding Element within the Human p16 Promoter".journal of biological chemistry (2010).