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https://hdl.handle.net/2440/133464
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Type: | Journal article |
Title: | DNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation patterns |
Author: | Skvortsova, K. Masle-Farquhar, E. Luu, P.L. Song, J.Z. Qu, W. Zotenko, E. Gould, C.M. Du, Q. Peters, T.J. Colino-Sanguino, Y. Pidsley, R. Nair, S.S. Khoury, A. Smith, G.C. Miosge, L.A. Reed, J.H. Kench, J.G. Rubin, M.A. Horvath, L. Bogdanovic, O. et al. |
Citation: | Cancer Cell, 2019; 35(2):297-314.e8 |
Publisher: | Elsevier BV |
Issue Date: | 2019 |
ISSN: | 1535-6108 1878-3686 |
Statement of Responsibility: | Ksenia Skvortsova, Etienne Masle-Farquhar, Phuc-Loi Luu, Jenny Z.Song, Wenjia Qu, Elena Zotenko ... et al. |
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. |
Keywords: | CpG islands; hypermethylation; DNA methylation encroachment; cancer; H3K4 monomethylation; BisChIP-seq; WGBS; TAB-seq; 5-hydroxymethylation |
Rights: | © 2019 Elsevier Inc. |
DOI: | 10.1016/j.ccell.2019.01.004 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1088144 http://purl.org/au-research/grants/nhmrc/1063559 |
Published version: | http://dx.doi.org/10.1016/j.ccell.2019.01.004 |
Appears in Collections: | Genetics publications |
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