Shared and Distinct Functions of the Transcription Factors IRF4 and IRF8 in Myeloid Cell Development 英文参考文献.docVIP
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Shared and Distinct Functions of the Transcription Factors IRF4 and IRF8 in Myeloid Cell Development 英文参考文献
SharedandDistinctFunctionsoftheTranscription
FactorsIRF4andIRF8inMyeloidCellDevelopment
MichioYamamoto1.,TakayukiKato2.,ChieHotta1,AkiraNishiyama1,DaisukeKurotaki1 ,Masahiro
Yoshinari1,MasamichiTakami3,MotohideIchino1,MasatoshiNakazawa4,ToshifumiMatsuyama5,
RyutaroKamijo3,SeiichiKitagawa2,KeikoOzato6,TomohikoTamura1,2,6*
1DepartmentofImmunology,YokohamaCityUniversityGraduateSchoolofMedicine,Yokohama,Japan,2DepartmentofPhysiology,OsakaCityUniversityGraduate
School ofMedicine, Osaka, Japan, 3Department of Biochemistry, School ofDentistry,Showa University, Tokyo, Japan, 4DepartmentofExperimental Animal Science,
YokohamaCityUniversityGraduateSchoolofMedicine,Yokohama,Japan,5DepartmentofMolecularMicrobiologyandImmunology,GraduateSchoolofBiomedical
Sciences, Nagasaki University, Nagasaki, Japan, 6Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human
Development,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica
Abstract
Interferon regulatory factor (IRF) 8 and IRF4 are structurally-related, hematopoietic cell-specific transcription factors that
cooperativelyregulatethedifferentiationofdendriticcellsandBcells.WhilstinmyeloidcellsIRF8isknowntomodulate
growthanddifferentiation,theroleofIRF4ispoorlyunderstood.Inthisstudy,weshowthatIRF4hasactivitiessimilarto
IRF8inregulatingmyeloidcelldevelopment.TheectopicexpressionofIRF4inmyeloidprogenitorcellsinvitroinhibitscell
growth,promotesmacrophages,buthindersgranulocyticcelldifferentiation.WealsoshowthatIRF4bindstoandactivates
transcriptionthroughtheIRF-Etscompositesequence(IECS).Furthermore,wedemonstratethatIrf8-/-Irf4-/-miceexhibita
more severe chronic myeloid leukemia (CML)-like disease than Irf8-/- mice, involving a disproportionate expansion of
granulocytesattheexpenseofmonocytes/macrophages.Irf4-/-mice,however,displaynoobviousabnormalityinmyeloid
cell development, presumably because IRF4 is expressed at a much lower level than IRF8 in granulocyte-macrophage
p
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