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学科主题临床医学
Nucleosomes Correlate with In Vivo Progression Pattern of De Novo Methylation of p16 CpG Islands in Human Gastric Carcinogenesis
Lu, Zhe-Ming1; Zhou, Jing1; Wang, Xiuhong1; Guan, Zhenpo1; Bai, Hua1; Liu, Zhao-Jun1; Su, Na1; Pan, Kaifeng2; Ji, Jiafu3; Deng, Dajun1
刊名PLOS ONE
2012-04-25
DOI10.1371/journal.pone.0035928
7期:4
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; National Natural Science Foundation of China ; National Basic Research Program of China
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]ABERRANT DNA METHYLATION ; CHROMATIN ACCESSIBILITY ; HUMAN CANCERS ; HUMAN TISSUES ; GENE ; P16(INK4A) ; INHIBITION ; OCCUPANCY ; DYSPLASIA ; POSITIONS
英文摘要

Background: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown.

Methodology/Principal Findings: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP) assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation "seeding′′ sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC) samples (36/40) was significantly higher than that observed in gastritis (19/45) or normal samples (7/13) (P < 0.01). Extensive clone sequencing of these sMSP products showed that the density of methylated-CpGs in p16 CpG islands increased gradually along with the severity of pathological changes in gastric tissues. In gastritis lesions the methylation was frequently observed in the region corresponding to the exon-1 coding-nucleosome and the 5′UTR-nucleosome; the methylation was further extended to the region corresponding to the promoter-nucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal tissues. The significantly inversed relationship between the p16 exon-1 methylation and its transcription was observed in GC samples. An exact p16 promoter-specific 83 bp-MSP assay confirms the result of sMSP (33/55 vs. 1/6, P < 0.01). In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens.

Conclusions/Significance: It was determined that de novo methylation was initiated in the coding region of p16 exon-1 in gastritis, then progressed to its 5′UTR, and ultimately to the proximal promoter in GCs. Nucleosomes may function as the basic extension/progression unit of de novo methylation of p16 CpG islands in vivo.

语种英语
所属项目编号90919015 ; 81071630 ; 30921140311 ; 2010CB529303 ; 2011CB504201
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号WOS:000305345200094
引用统计
被引频次:12[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/400002259/64020
专题北京大学临床肿瘤学院_流行病学研究室
作者单位1.Peking Univ, Key Lab Carcinogenesis & Translat Res, Canc Hosp & Inst, Minist Educ,Div Canc Etiol, Beijing 100871, Peoples R China
2.Peking Univ, Canc Hosp & Inst, Dept Epidemiol, Beijing 100871, Peoples R China
3.Peking Univ, Canc Hosp & Inst, Dept Surg, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Lu, Zhe-Ming,Zhou, Jing,Wang, Xiuhong,et al. Nucleosomes Correlate with In Vivo Progression Pattern of De Novo Methylation of p16 CpG Islands in Human Gastric Carcinogenesis[J]. PLOS ONE,2012,7(4).
APA Lu, Zhe-Ming.,Zhou, Jing.,Wang, Xiuhong.,Guan, Zhenpo.,Bai, Hua.,...&Deng, Dajun.(2012).Nucleosomes Correlate with In Vivo Progression Pattern of De Novo Methylation of p16 CpG Islands in Human Gastric Carcinogenesis.PLOS ONE,7(4).
MLA Lu, Zhe-Ming,et al."Nucleosomes Correlate with In Vivo Progression Pattern of De Novo Methylation of p16 CpG Islands in Human Gastric Carcinogenesis".PLOS ONE 7.4(2012).
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