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Functional Enhancers at the Gene-Poor 8q24 Cancer-Linked Locus 英文参考文献
FunctionalEnhancersattheGene-Poor8q24Cancer-
LinkedLocus
LiJia1,2.,GiladLandan3.,MarkPomerantz4,RamiJaschek3,PaulaHerman4,DavidReich5,ChunliYan1,
OmarKhalid1,2,PhilKantoff4,WilliamOh4,J.RobertManak6,BenjaminP.Berman7,BrianE.Henderson1,
BaruchFrenkel8,ChristopherA.Haiman1,MatthewFreedman4,9,AmosTanay3*,GerhardA.Coetzee1,2*
1USC/NorrisCancerCenter,Department ofPreventive Medicine, University ofSouthernCalifornia,Los Angeles,California,United States ofAmerica,2Department of
Urology,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica,3DepartmentofComputerScienceandAppliedMathematics,Weizmann
InstituteofScience,Rehovot,Israel,4Dana-FarberCancerInstitute,DepartmentofMedicalOncology,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesof
America,5DepartmentofGenetics,HarvardMedicalSchool,Boston, Massachusetts,UnitedStatesofAmerica,6DepartmentofBiology,UniversityofIowa,IowaCity,
Iowa,UnitedStatesofAmerica,7USC/EpigenomeCenter,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica,
8DepartmentofOrthopedicSurgeryandDepartmentofBiochemistryandMolecularBiology,InstituteofGeneticMedicine,UniversityofSouthernCalifornia,LosAngeles,
California,UnitedStatesofAmerica,9BroadInstituteofHarvardandMIT,Cambridge,Massachusetts,UnitedStatesofAmerica
Abstract
Multiplediscreteregionsat8q24wererecentlyshowntocontainallelesthatpredisposetomanycancersincludingprostate,
breast,andcolon.Theseregionsarefarfromanyannotatedgeneandtheirbiologicalactivitieshavebeenunknown.Here
weprofileda5-megabasechromatinsegmentencompassingalltheriskregionsforRNAexpression,histonemodifications,
and locations occupied by RNA polymerase II and androgen receptor (AR). This led to the identification of several
transcriptionalenhancers,whichwereverifiedusingreporterassays.TwoenhancersinoneriskregionwereoccupiedbyAR
andrespondedtoandrogentreatment;onecontainedasinglenucleotidepolymorphism(rthatresideswithina
FoxA1 binding site, with the pr
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