Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.
Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.
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DOI：
10.1371/journal.pone.0035928
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Deng D
中科院分区：
文献类型：
--
作者：
Lu ZM;Zhou J;Wang X;Guan Z;Bai H;Liu ZJ;Su N;Pan K;Ji J;Deng D
The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. 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. 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.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
6.1
作者：
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Xin, HJ
DOI：
10.1016/s1383-5718(02)00288-7
发表时间：
2003-02-05
影响因子：
1.9
作者：
Bai, H;Gu, LK;Deng, DJ
通讯作者：
Deng, DJ
哺乳动物启动子的足迹：使用CpG DNA甲基转移酶在单个分子水平上揭示了核小体位置。
影响因子：
14.9
作者：
Fatemi, M;Pao, MM;Jeong, S;Gal-Yam, EN;Egger, G;Weisenberger, DJ;Jones, PA
通讯作者：
Jones, PA
DOI：
10.1073/pnas.95.20.11891
发表时间：
1998-09-29
影响因子：
11.1
作者：
Belinsky, SA;Nikula, KJ;Herman, JG
通讯作者：
Herman, JG