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Epigenetic interplay between mouse endogenous retroviruses and host genes.doc

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Epigenetic interplay between mouse endogenous retroviruses and host genes

Rebolloetal.GenomeBiology2012,13:R89 /2012/13/10/R89 RESEARCH OpenAccess Epigeneticinterplaybetweenmouseendogenous retrovirusesandhostgenes RitaRebollo1,2?,KatharineMiceli-Royer1,2?,YingZhang1,2,ShararehFarivar1,2,LianeGagnier1,2 andDixieLMager1,2* Abstract Background:TransposableelementsareoftenthetargetsofrepressiveepigeneticmodificationssuchasDNA methylationthat,intheory,havethepotentialtospreadtowardnearbygenesandinduceepigeneticsilencing. TobetterunderstandtheroleofDNAmethylationintherelationshipbetweentransposableelementsandgenes, weassessedthemethylationstateofmouseendogenousretroviruses(ERVs)locatedneargenes. Results:WefoundthatERVsoftheETn/MusDfamilyshowdecreasedDNAmethylationwhenneartranscription startsitesintissueswherethenearbygeneisexpressed.ERVsbelongingtotheIAPfamily,however,aregenerally heavilymethylated,regardlessofthegenomicenvironmentandthetissuestudied.Furthermore,wefoundfull- lengthETnandIAPcopiesthatdisplaydifferentialDNAmethylationbetweentheirtwolongterminalrepeats (LTRs),suggestingthattheenvironmentsurroundinggenepromoterscanpreventmethylationofthenearbyLTR. SpreadingfrommethylatedERVcopiestonearbygeneswasrarelyobserved,withtheregionsbetweentheERVs andgenesapparentlyactingasaboundary,enrichedinH3K4me3andCTCF,whichpossiblyprotectsthe unmethylatedgenepromoter.Furthermore,theflankingregionsofunmethylatedERVcopiesharborH3K4me3, consistentwithspreadingofeuchromatinfromthehostgenetowardERVinsertions. Conclusions:WehaveshownthatspreadingofDNAmethylationfromERVcopiestowardactivegenepromoters israre.WeprovideevidencethatgenescanbeprotectedfromERV-inducedheterochromatinspreadingbyeither blockingtheinvasionofrepressivemarksorbyspreadingeuchromatintowardtheERVcopy. Keywords:DNAmethylation,epigenetics,evolution,heterochromatinspreading,mouseendogenousretroviruses, transposableelement Background been shown that mutants of the DNA methylation Transposableelements(TEs)areDNAsequencesableto machinery induce bursts of transposition of usually movef