Obesity Risk Gene TMEM18 Encodes a Sequence-Specific DNA-Binding Protein 英文参考文献.docVIP

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Obesity Risk Gene TMEM18 Encodes a Sequence-Specific DNA-Binding Protein 英文参考文献.doc

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Obesity Risk Gene TMEM18 Encodes a Sequence-Specific DNA-Binding Protein 英文参考文献

ObesityRiskGeneTMEM18EncodesaSequence-Specific DNA-BindingProtein JaanaM.Jurvansuu*,AdrianGoldman StructuralBiologyandBiophysics,InstituteofBiotechnology,UniversityofHelsinki,Helsinki,Finland Abstract Transmembraneprotein18(TMEM18)haspreviouslybeenconnectedtocellmigrationandobesity.However,themolecular functionoftheproteinhasnotyetbeendescribed.HereweshowthatTMEM18localisestothenuclearmembraneand bindstoDNAinasequence-specificmanner.TheproteinbindsDNAwithitspositivelychargedC-terminusthatcontains alsoanuclearlocalisationsignal.IncreaseintheamountofTMEM18incellssuppressesexpressionfromareportervector withtheTMEM18targetsequence.TMEM18isasmallproteinof140residuesandispredictedtobemostlyalpha-helical withthreetransmembraneparts.AsaconsequencetheDNAbindingbyTMEM18wouldbringthechromatinverynearto nuclear membrane. We speculate that this closed perinuclear localisation of TMEM18-bound DNA might repress transcriptionfromit. Citation:JurvansuuJM,GoldmanA(2011)ObesityRiskGeneTMEM18EncodesaSequence-SpecificDNA-BindingProtein.PLoSONE6(9):e25317.doi:10.1371/ journal.pone.0025317 Editor:BrianP.Chadwick,FloridaStateUniversity,UnitedStatesofAmerica ReceivedJune28,2011;AcceptedAugust31,2011;PublishedSeptember28,2011 Copyright:?2011Jurvansuu,Goldman.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported by Academy of Finland (1128207 to J.M.J., 1114752 to A.G., www.aka.fi); and the Sigrid Juse′lius Foundation (www. sigridjuselius.fi).Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:jaana.jurvansuu@helsinki.fi Introduction TMEM18 is a small protein of 140 amino acids. It has a functional nuclear localisation signal and it is predicted to have threetransmembranehelic