Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation 英文参考文献.docVIP

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Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation 英文参考文献.doc

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Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation 英文参考文献

Pregnancy-InducedNoncodingRNA(PINC)Associates withPolycombRepressiveComplex2andRegulates MammaryEpithelialDifferentiation AmyN.Shore1,ElenaB.Kabotyanski2,KevinRoarty2,MartinA.Smith3,YiqunZhang4, ChadJ.Creighton4,MarcelE.Dinger5,JeffreyM.Rosen1,2* 1Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America, 2Department of Molecular and Cellular Biology, Baylor CollegeofMedicine,Houston,Texas,UnitedStatesofAmerica,3InstituteforMolecularBioscience,TheUniversityofQueensland,Brisbane,Australia,4DanL.Duncan CancerCenter,BaylorCollegeofMedicine,Houston,Texas,UnitedStatesofAmerica,5DiamantinaInstitute,TheUniversityofQueensland,PrincessAlexandraHospital, Brisbane,Australia Abstract Pregnancy-inducednoncodingRNA(PINC)andretinoblastoma-associatedprotein46(RbAp46)areupregulatedinalveolar cellsofthemammaryglandduringpregnancyandpersistinalveolarcellsthatremainintheregressedlobulesfollowing involution.Thecellsthatsurviveinvolutionarethoughttofunctionasalveolarprogenitorcellsthatrapidlydifferentiateinto milk-producingcellsinsubsequentpregnancies,butitisunknownwhetherPINCandRbAp46areinvolvedinmaintaining thisprogenitorpopulation.Here,weshowthat,inthepost-pubertalmousemammarygland,mPINCisenrichedinluminal andalveolarprogenitors.mPINClevelsincreasethroughoutpregnancyandthendeclineinearlylactation,whenalveolar cells undergo terminal differentiation. Accordingly, mPINC expression is significantly decreased when HC11 mammary epithelialcellsareinducedtodifferentiateandproducemilkproteins.ThisreductioninmPINClevelsmaybenecessaryfor lactation,asoverexpressionofmPINCinHC11cellsblockslactogenicdifferentiation,whileknockdownofmPINCenhances differentiation. Finally, we demonstrate that mPINC interacts with RbAp46, as well as other members of the polycomb repressivecomplex2(PRC2),andidentifypotentialtargetsofmPINCthataredifferentiallyexpressedfollowingmodulation ofmPINCexpressionlevels.Takentogether,ourdatasuggestthatmPINCinhibitsterminaldifferentiati