| Title: |
DNA Hypermethylation Encroachment at CpG Island Borders in Cancer Is Predisposed by H3K4 Monomethylation Patterns |
| Authors: |
Skvortsova, Ksenia; Masle-Farquhar, Etienne; Luu, Phuc-Loi; Song, Jenny Z; Qu, W; Zotenko, Elena; Gould, Cathryn M.; Du, Qian; Peters, Timothy J.; Colino-Sanguino, Yolanda; Miosge, Lisa; Reed, Joanne; Goodnow, Christopher; Nair, Shalima S; Horvath, Lisa G.; Polo, Jose M |
| Source: |
Cancer Cell |
| Publisher Information: |
Cell Press |
| Publication Year: |
2021 |
| Collection: |
Australian National University: ANU Digital Collections |
| Subject Terms: |
CpG islands; hypermethylation; DNA methylation encroachment; cancer; H3K4 monomethylation; BisChIP-seq; WGBS; TAB-seq; 5-hydroxymethylation |
| Description: |
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. ; We thank the Wysocka Laboratory for the generous gift of wild-type and mutant mESCs (Dorighi et al., 2017) and Roger Daly for financial support of prostate cancer WGBS (Cancer Institute NSW, Australia, program grant).The Bill and Patricia Ritchie Foundation, Australia (C.C.G.); UNSW Sydney University International Postgraduate Award (UIPA), Australia (K.S.) |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
http://purl.org/au-research/grants/nhmrc/1088144; http://purl.org/au-research/grants/nhmrc/1063559; http://purl.org/au-research/grants/nhmrc/1113904; http://purl.org/au-research/grants/nhmrc/1081858; https://hdl.handle.net/1885/281470 |
| DOI: |
10.1016/j.ccell.2019.01.004 |
| Availability: |
https://hdl.handle.net/1885/281470; https://doi.org/10.1016/j.ccell.2019.01.004; https://openresearch-repository.anu.edu.au/bitstreams/eaa1359b-c3c0-404f-9473-7fd6d5c1f11f/download; https://openresearch-repository.anu.edu.au/bitstreams/76f1eda3-3535-4569-bd80-b70cf6ebfc55/download |
| Rights: |
© 2019 The authors |
| Accession Number: |
edsbas.256B432D |
| Database: |
BASE |