Global Methylation Patterns in Idiopathic Pulmonary Fibrosis 英文参考文献.docVIP

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Global Methylation Patterns in Idiopathic Pulmonary Fibrosis 英文参考文献.doc

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Global Methylation Patterns in Idiopathic Pulmonary Fibrosis 英文参考文献

GlobalMethylationPatternsinIdiopathicPulmonary Fibrosis EinatI.Rabinovich1,MariaG.Kapetanaki1,IsraelSteinfeld2,KevinF.Gibson1,KusumV.Pandit1, GuoyingYu1,ZoharYakhini2,3,NaftaliKaminski1* 1DorothyP.andRichardP.SimmonsCenterforInterstitialLungDisease,DivisionofPulmonary,AllergyandCriticalCareMedicine,UniversityofPittsburgh,Schoolof Medicine, Pittsburgh, Pennsylvania, United States of America, 2Department of Computer Sciences, Technion – Israel Institute of Technology, Haifa, Israel, 3Agilent Laboratories,Tel-Aviv,Israel Abstract Background: Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessiveextracellularmatrixdeposition,myofibroblastfoci,alveolarepithelialcellhyperplasiaandextensiveremodeling. TheroleofepigeneticchangesindeterminingthelungphenotypeinIPFisunknown.Inthisstudywedeterminewhether IPFlungsexhibitanalteredglobalmethylationprofile. Methodology/PrincipalFindings:ImmunoprecipitatedmethylatedDNAfrom12IPFlungs,10lungadenocarcinomasand 10normalhistologylungswashybridizedtoAgilenthumanCpGIslandsMicroarraysanddataanalysiswasperformedusing BRB-ArrayToolsandDAVIDBioinformaticsResourcessoftwarepackages.ArrayresultswerevalidatedusingtheEpiTYPER MassARRAYplatformfor3CpGislands.625CpGislandsweredifferentiallymethylatedbetweenIPFandcontrollungswith anestimatedFalseDiscoveryRatelessthan5%.ThegenesassociatedwiththedifferentiallymethylatedCpGislandsare involved in regulation of apoptosis, morphogenesis and cellular biosynthetic processes. The expression of three genes (STK17B,STK3andHIST1H2AH)withhypomethylatedpromoterswasincreasedinIPFlungs.ComparisonofIPFmethylation patternstolungcancerorcontrolsamples,revealedthatIPFlungsdisplayanintermediatemethylationprofile,partlysimilar tolung cancerandpartlysimilartocontrolwith402differentiallymethylated CpGislandsoverlappingbetweenIPFand cancer.Despitetheirsimilaritytocancer,IPFlungsdidnotexhibithypomethylationoflonginterspersednuclearelement1 (LINE-1)retrotranspos