Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.

PloS One
Zhe-Ming LuDajun Deng

Abstract

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 tran...Continue Reading

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Citations

May 2, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Chen YangDajun Deng
Feb 15, 2014·The American Journal of Pathology·Natalie C Silmon de Monerri, Kami Kim
Jun 9, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xuan WangTing-Ting Yu
Jul 29, 2016·Cellular and Molecular Life Sciences : CMLS·Jun TieDaiming Fan
Jul 29, 2016·Scientific Reports·Toshitsugu FujitaHodaka Fujii
Feb 14, 2015·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Liang ZongToshikazu Ushijima

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Methods Mentioned

BETA
PCR
biopsies
biopsy
immunoprecipitation

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