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IR@PKUHSC  > 北京大学临床肿瘤学院  > 流行病学研究室  > 期刊论文
学科主题: 临床医学
题名:
Nucleosomes Correlate with In Vivo Progression Pattern of De Novo Methylation of p16 CpG Islands in Human Gastric Carcinogenesis
作者: 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
发表日期: 2012-04-25
DOI: 10.1371/journal.pone.0035928
卷: 7, 期:4
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
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
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号: WOS:000305345200094
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64020
Appears in Collections:北京大学临床肿瘤学院_流行病学研究室_期刊论文

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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

Recommended Citation:
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).
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