Cargando…

Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer

The highly repetitive Alu retroelements are regarded as methylation centres in the genome. Methylation in the gene promoters could be spreading from them. Promoter methylation of MLH1 is frequently detected in cancers, but the underlying mechanism is unclear. The aim of this study is to understand w...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xiyin, Fan, Jing, Liu, Dong, Fu, Siqing, Ingvarsson, Sigurdur, Chen, Huiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192117/
https://www.ncbi.nlm.nih.gov/pubmed/22022465
http://dx.doi.org/10.1371/journal.pone.0025913
_version_ 1782213712934862848
author Wang, Xiyin
Fan, Jing
Liu, Dong
Fu, Siqing
Ingvarsson, Sigurdur
Chen, Huiping
author_facet Wang, Xiyin
Fan, Jing
Liu, Dong
Fu, Siqing
Ingvarsson, Sigurdur
Chen, Huiping
author_sort Wang, Xiyin
collection PubMed
description The highly repetitive Alu retroelements are regarded as methylation centres in the genome. Methylation in the gene promoters could be spreading from them. Promoter methylation of MLH1 is frequently detected in cancers, but the underlying mechanism is unclear. The aim of this study is to understand whether the methylation in the Alu elements is associated with promoter methylation in the MLH1 gene. Bisulfite genomic sequencing was used to analyse the CpG sites of the 5′ end (promoter, exon 1 and Alu-containing intron 1) of the MLH1 gene in colorectal cancer cells and tissues, and gastric cancer tissues. Hypomethylation in the Alu elements and hypermethylation in the promoters and the regions between the promoters and the Alu elements were detected in two cancer cell lines and seven cancer tissues. However, demethylation or hypomethylation of the MLH1 promoter and regions between promoter and the Alu elements, and hypermethylation in the Alu elements, were identified in the normal tissues. MLH1 promoter methylation may spread from Alu elements that are located in intron 1 of the MLH1 gene. The trans-acting elements binding to the mutation sites could play a role in the methylation spreading.
format Online
Article
Text
id pubmed-3192117
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-31921172011-10-21 Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer Wang, Xiyin Fan, Jing Liu, Dong Fu, Siqing Ingvarsson, Sigurdur Chen, Huiping PLoS One Research Article The highly repetitive Alu retroelements are regarded as methylation centres in the genome. Methylation in the gene promoters could be spreading from them. Promoter methylation of MLH1 is frequently detected in cancers, but the underlying mechanism is unclear. The aim of this study is to understand whether the methylation in the Alu elements is associated with promoter methylation in the MLH1 gene. Bisulfite genomic sequencing was used to analyse the CpG sites of the 5′ end (promoter, exon 1 and Alu-containing intron 1) of the MLH1 gene in colorectal cancer cells and tissues, and gastric cancer tissues. Hypomethylation in the Alu elements and hypermethylation in the promoters and the regions between the promoters and the Alu elements were detected in two cancer cell lines and seven cancer tissues. However, demethylation or hypomethylation of the MLH1 promoter and regions between promoter and the Alu elements, and hypermethylation in the Alu elements, were identified in the normal tissues. MLH1 promoter methylation may spread from Alu elements that are located in intron 1 of the MLH1 gene. The trans-acting elements binding to the mutation sites could play a role in the methylation spreading. Public Library of Science 2011-10-12 /pmc/articles/PMC3192117/ /pubmed/22022465 http://dx.doi.org/10.1371/journal.pone.0025913 Text en Wang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Xiyin
Fan, Jing
Liu, Dong
Fu, Siqing
Ingvarsson, Sigurdur
Chen, Huiping
Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer
title Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer
title_full Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer
title_fullStr Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer
title_full_unstemmed Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer
title_short Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer
title_sort spreading of alu methylation to the promoter of the mlh1 gene in gastrointestinal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192117/
https://www.ncbi.nlm.nih.gov/pubmed/22022465
http://dx.doi.org/10.1371/journal.pone.0025913
work_keys_str_mv AT wangxiyin spreadingofalumethylationtothepromoterofthemlh1geneingastrointestinalcancer
AT fanjing spreadingofalumethylationtothepromoterofthemlh1geneingastrointestinalcancer
AT liudong spreadingofalumethylationtothepromoterofthemlh1geneingastrointestinalcancer
AT fusiqing spreadingofalumethylationtothepromoterofthemlh1geneingastrointestinalcancer
AT ingvarssonsigurdur spreadingofalumethylationtothepromoterofthemlh1geneingastrointestinalcancer
AT chenhuiping spreadingofalumethylationtothepromoterofthemlh1geneingastrointestinalcancer