| Literature DB >> 30753827 |
Ksenia Skvortsova1, Etienne Masle-Farquhar2, Phuc-Loi Luu3, Jenny Z Song3, Wenjia Qu3, Elena Zotenko3, Cathryn M Gould3, Qian Du3, Timothy J Peters3, Yolanda Colino-Sanguino3, Ruth Pidsley3, Shalima S Nair3, Amanda Khoury3, Grady C Smith3, Lisa A Miosge4, Joanne H Reed2, James G Kench5, Mark A Rubin6, Lisa Horvath7, Ozren Bogdanovic8, Sue Mei Lim9, Jose M Polo9, Christopher C Goodnow10, Clare Stirzaker11, Susan J Clark12.
Abstract
Promoter CpG islands are typically unmethylated in normal cells, but in cancer a proportion are subject to hypermethylation. Using methylome sequencing we identified CpG islands that display partial methylation encroachment across the 5' or 3' CpG island borders. CpG island methylation encroachment is widespread in prostate and breast cancer and commonly associates with gene suppression. We show that the pattern of H3K4me1 at CpG island borders in normal cells predicts the different modes of cancer CpG island hypermethylation. Notably, genetic manipulation of Kmt2d results in concordant alterations in H3K4me1 levels and CpG island border DNA methylation encroachment. Our findings suggest a role for H3K4me1 in the demarcation of CpG island methylation borders in normal cells, which become eroded in cancer.Entities:
Keywords: 5-hydroxymethylation; BisChIP-seq; CpG islands; DNA methylation encroachment; H3K4 monomethylation; TAB-seq; WGBS; cancer; hypermethylation
Year: 2019 PMID： 30753827 DOI： 10.1016/j.ccell.2019.01.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743