Mechanisms of Dietary Response in Mice and Primates A Role for EGR1 in Regulating the Reaction to Human-Specific Nutritional Content 英文参考文献.docVIP

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Mechanisms of Dietary Response in Mice and Primates A Role for EGR1 in Regulating the Reaction to Human-Specific Nutritional Content 英文参考文献.doc

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Mechanisms of Dietary Response in Mice and Primates A Role for EGR1 in Regulating the Reaction to Human-Specific Nutritional Content 英文参考文献

MechanismsofDietaryResponseinMiceandPrimates:A RoleforEGR1inRegulatingtheReactiontoHuman- SpecificNutritionalContent KaiWeng1,HaiyangHu1,AugixGuohuaXu1,2,PhilippKhaitovich1,2*,MehmetSomel1,2,3 * 1KeyLaboratoryofComputationalBiology,CAS-MPGPartnerInstituteforComputationalBiology,ChineseAcademyofSciences,Shanghai,China,2MaxPlanckInstitute forEvolutionaryAnthropology,Leipzig,Germany,3DepartmentofIntegrativeBiology,UniversityofCalifornia,Berkeley,California,UnitedStatesofAmerica Abstract Background:Humanshaveawidelydifferentdietfromotherprimatespecies,andaredependentonitshighnutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzeedietsinvolvesthesameregulatorymechanismsasexpressiondifferencesbetweenhumansandchimpanzees. Results:Usingmouseandprimatetranscriptomicdata,weidentifiedthetranscriptionfactorEGR1(earlygrowthresponse1) asaputativeregulatorofdiet-relateddifferentialgeneexpressionbetweenhumanandchimpanzeelivers.Specifically,we predictthatEGR1regulatestheresponsetothehighcaloriccontentofhumandiets.However,wealsoshowthatcloseto 90%ofthedietaryresponsetotheprimatedietfoundinmice,isnotobservedinprimates.Thismightbeexplainedby changesintissue-specificgeneexpressionbetweentaxa. Conclusion:Ourresultssuggestthatthegeneexpressionresponsetothenutritionallyrichhumandietispartiallymediated bythetranscriptionfactorEGR1.WhilethisEGR1-drivenresponseisconservedbetweenmiceandprimates,thebulkofthe mouseresponsetohumanandchimpanzeedietarydifferencesisnotobservedinprimates.Thisresulthighlightstherapid evolutionofdiet-relatedexpressionregulationandunderscorespotentiallimitationsofmousemodelsindietarystudies. Citation:WengK,HuH,XuAG,KhaitovichP,SomelM(2012)MechanismsofDietaryResponseinMiceandPrimates:ARoleforEGR1inRegulatingtheReaction toHuman-SpecificNutritionalContent.PLoSONE7(8):e43915.doi:10.1371/j