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1、Ó2011Wiley-Liss,Inc.BirthDefectsResearch(PartA)91:770780(2011)ReviewArticleDiabeticembryopathy:Arolefortheepigenome?J.MichaelSalbaum*andClaudiaKappenPenningtonBiomedicalResearchCenter,BatonRouge,LouisianaReceived11October2010;Revised4February2011;Accepted11February2011Embryonicdevelopmentundera
2、dverseconditions,suchasmaternaldiabetesorobesityduringpregnancy,constitutesamajorriskfactorforbirthdefects,aswellasforlong-termhealthconsequencesanddiseasesus-ceptibilityintheoffspring.Whilecontributionsfromepigeneticchangeshavebeeninvokedpreviouslytoexplainthelong-termchangesintermsofdevelopmen
3、talprogramming,weherereviewhowmaternalmetab-olismmaydirectlyaffecttheembryonicepigenomeinrelationshiptoteratogenicprocesses.Weconsiderfourepigeneticmodalities–DNAmethylation,non-codingRNA,transcriptionfactors,andhistonemodifications–andtheircontributiontoepigeneticmemory,anddiscusshowepigenomicch
4、angesmaymediatethealteredcon-trolofembryonicgeneexpressionbroughtaboutbymaternaldiabetes.Incombination,theepigenomicmodal-itiesservetodefinetranscription-permissivedomainsofthegenome,resultingindistinctepigenomiclandscapesindifferentdevelopmentalcelltypes.Weevaluateexperimentalapproachestocharact
5、erizetheepigenomeinadversepregnancyconditions,highlightingtheroleofnext-generationsequencingonthetechnologicalside,whileemphasizingthenecessitytostudydefinedcellpopulationsintermsofbiologicimpact.Finally,weoutlinethechallengesinmovingfromfindingsthatcorrelateepigenomicstodevelopmentalphenotypestos
6、cenariosthatestablishteratogeniccausality.BirthDefectsResearch(PartA)91:770–780,2011.Ó2011Wiley-Liss,Inc.INTRODUCTIONorgestationaldiabetes(Kousseff,1999).Diabeticembry-Pregnancyunderadverseconditionsopathycanaffectmanyorgansystems(Mills,1982;GotoandGoldman,1994;Martinez-Frias,1994;Cassonetal.,In
7、thepastfewyears,thecatchphrase‘‘youarewhat1997;Abergetal.,2001),butthemostcommonmal-yourmothereats’’hasbeengainingwidespreadattentionformationsaffecttheheart(Loffredoetal.,2001)ortheinthepublic,mostlikelyduetoitssimplicity,a
