DNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation patterns

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dc.contributor.authorSkvortsova, K.
dc.contributor.authorMasle-Farquhar, E.
dc.contributor.authorLuu, P.L.
dc.contributor.authorSong, J.Z.
dc.contributor.authorQu, W.
dc.contributor.authorZotenko, E.
dc.contributor.authorGould, C.M.
dc.contributor.authorDu, Q.
dc.contributor.authorPeters, T.J.
dc.contributor.authorColino-Sanguino, Y.
dc.contributor.authorPidsley, R.
dc.contributor.authorNair, S.S.
dc.contributor.authorKhoury, A.
dc.contributor.authorSmith, G.C.
dc.contributor.authorMiosge, L.A.
dc.contributor.authorReed, J.H.
dc.contributor.authorKench, J.G.
dc.contributor.authorRubin, M.A.
dc.contributor.authorHorvath, L.
dc.contributor.authorBogdanovic, O.
dc.contributor.authoret al.
dc.date.issued2019
dc.description.abstractPromoter 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.
dc.description.statementofresponsibilityKsenia Skvortsova, Etienne Masle-Farquhar, Phuc-Loi Luu, Jenny Z.Song, Wenjia Qu, Elena Zotenko ... et al.
dc.identifier.citationCancer Cell, 2019; 35(2):297-314.e8
dc.identifier.doi10.1016/j.ccell.2019.01.004
dc.identifier.issn1535-6108
dc.identifier.issn1878-3686
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133464
dc.language.isoen
dc.publisherElsevier BV
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1088144
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1063559
dc.rights© 2019 Elsevier Inc.
dc.source.urihttps://doi.org/10.1016/j.ccell.2019.01.004
dc.subjectCpG islands; hypermethylation; DNA methylation encroachment; cancer; H3K4 monomethylation; BisChIP-seq; WGBS; TAB-seq; 5-hydroxymethylation
dc.subject.meshCell Line, Tumor
dc.subject.meshAnimals
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Knockout
dc.subject.meshHumans
dc.subject.meshNeoplasms
dc.subject.mesh5-Methylcytosine
dc.subject.meshHistone-Lysine N-Methyltransferase
dc.subject.meshDNA-Binding Proteins
dc.subject.meshNeoplasm Proteins
dc.subject.meshHistones
dc.subject.meshDNA, Neoplasm
dc.subject.meshDNA Methylation
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshCpG Islands
dc.subject.meshMethylation
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshMyeloid-Lymphoid Leukemia Protein
dc.subject.meshPromoter Regions, Genetic
dc.titleDNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation patterns
dc.typeJournal article
pubs.publication-statusPublished

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