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.
| Original language | English |
|---|---|
| Pages (from-to) | 297-314 |
| Number of pages | 18 |
| Journal | Cancer Cell |
| Volume | 35 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 11 Feb 2019 |
Keywords
- 5-hydroxymethylation
- BisChIP-seq
- cancer
- CpG islands
- DNA methylation encroachment
- H3K4 monomethylation
- hypermethylation
- TAB-seq
- WGBS
Cite this
}
DNA Hypermethylation Encroachment at CpG Island Borders in Cancer Is Predisposed by H3K4 Monomethylation Patterns. / Skvortsova, Ksenia; Masle-Farquhar, Etienne; Luu, Phuc Loi; Song, Jenny Z.; Qu, Wenjia; Zotenko, Elena; Gould, Cathryn M.; Du, Qian; Peters, Timothy J.; Colino-Sanguino, Yolanda; Pidsley, Ruth; Nair, Shalima S.; Khoury, Amanda; Smith, Grady C.; Miosge, Lisa A.; Reed, Joanne H.; Kench, James G.; Rubin, Mark A.; Horvath, Lisa; Bogdanovic, Ozren; Lim, Sue Mei; Polo, Jose M.; Goodnow, Christopher C.; Stirzaker, Clare; Clark, Susan J.
In: Cancer Cell, Vol. 35, No. 2, 11.02.2019, p. 297-314.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - DNA Hypermethylation Encroachment at CpG Island Borders in Cancer Is Predisposed by H3K4 Monomethylation Patterns
AU - Skvortsova, Ksenia
AU - Masle-Farquhar, Etienne
AU - Luu, Phuc Loi
AU - Song, Jenny Z.
AU - Qu, Wenjia
AU - Zotenko, Elena
AU - Gould, Cathryn M.
AU - Du, Qian
AU - Peters, Timothy J.
AU - Colino-Sanguino, Yolanda
AU - Pidsley, Ruth
AU - Nair, Shalima S.
AU - Khoury, Amanda
AU - Smith, Grady C.
AU - Miosge, Lisa A.
AU - Reed, Joanne H.
AU - Kench, James G.
AU - Rubin, Mark A.
AU - Horvath, Lisa
AU - Bogdanovic, Ozren
AU - Lim, Sue Mei
AU - Polo, Jose M.
AU - Goodnow, Christopher C.
AU - Stirzaker, Clare
AU - Clark, Susan J.
PY - 2019/2/11
Y1 - 2019/2/11
N2 - 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.
AB - 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.
KW - 5-hydroxymethylation
KW - BisChIP-seq
KW - cancer
KW - CpG islands
KW - DNA methylation encroachment
KW - H3K4 monomethylation
KW - hypermethylation
KW - TAB-seq
KW - WGBS
UR - http://www.scopus.com/inward/record.url?scp=85060889507&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2019.01.004
DO - 10.1016/j.ccell.2019.01.004
M3 - Article
VL - 35
SP - 297
EP - 314
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 2
ER -