Direct ChIP-bisulfite sequencing reveals a role of H3K27me3 mediating aberrant hypermethylation of promoter CpG islands in cancer cells

摘要

ThemodeldescribingthataberrantCpGisland(CGI)methylationleadstorepressionoftumoursuppressorgenesincancershasbeeninfluential,butitremainsunclearhowsuchaberrancyisinduced.RecentstudiesprovidedcluesindicatingthatpromoterhypermethylationincancersmightbeassociatedwithPRCtargetgenes.Here,weusedChIP-BS-seqtoexaminemethylationoftheDNAfragmentsprecipitatedbytheantibodiestobothH3K27me3andH3K4me3histonemodifications.Weshowedthat,forasetofgeneshighlyenrichedwithH3K27me3bothincancerandnormalcells,CGIpromoterswereaberrantlyhypermethylatedonlyincancercellsincomparisonwithnormalcells.Incontrast,suchaberrantCGIhypermethylationincancerpromotersthatweredeficientofH3K27me3wasnotnotable.Furthermore,weconfirmedthatthesegeneswereconsistentlyhypermethylatedinTCGAprimarycancercells.TheseworkssupporttheassociationbetweenH3K27me3andDNAmethylationmarksforspecificcancergenesandwillspurfutureworkoncombinedhistoneandDNAmethylationthatcoulddefinecancer'sepigeneticabnormalities./p/div