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; ... (2019). DNA Hypermethylation Encroachment at CpG Island Borders in Cancer Is Predisposed by H3K4 Monomethylation Patterns. Cancer cell, 35(2), 297-314.e8. Cell Press 10.1016/j.ccell.2019.01.004

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Rubin, Mark Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1535-6108

Publisher:

Cell Press

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

19 Dec 2019 14:13

Last Modified:

19 Dec 2019 14:13

Publisher DOI:

10.1016/j.ccell.2019.01.004

PubMed ID:

30753827

Uncontrolled Keywords:

5-hydroxymethylation BisChIP-seq CpG islands DNA methylation encroachment H3K4 monomethylation TAB-seq WGBS cancer hypermethylation

BORIS DOI:

10.7892/boris.136284

URI:

https://boris.unibe.ch/id/eprint/136284

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