Definition of Regulatory Network Elements for T Cell Development by Perturbation Analysis with PU.1 and GATA-3

Developmental Biology

Ellen V. Rothenberg¹  Gabriela Hernandez-Hoyos¹  Dan Chen¹  Michele K. Anderson¹  Christopher J. Dionne¹  Alexandra M. Arias¹ 

[1] Division of Biology, California Institute of Technology, Pasadena, California, 91125

关键词: T cell development;    fetal thymus organ culture;    GATA-3;    PU.1;    Ets family;    retroviral transduction;    IL-7 receptor;    c-Myb;    HES-1;    pre-TCR;   

DOI  :  10.1006/dbio.2002.0674

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

PU.1andGATA-3aretranscriptionfactorsthatarerequiredfordevelopmentofTcellprogenitorsfromtheearlieststages.NeitheroneisasimplepositiveregulatorforTlineagespecification,however.WhenexpressedatelevatedlevelsatearlystagesofTcelldevelopment,eachofthesetranscriptionfactorsblocksTcelldevelopmentwithinadifferent,characteristictimewindow,withGATA-3overexpressioninitiallyinhibitingatanearlierstagethanPU.1.TheseperturbationsareeachassociatedwithadistinctspectrumofchangesintheregulationofgenesneededforTcelldevelopment.BothtranscriptionfactorscaninterferewithexpressionoftheRag-1andRag-2recombinases,whileGATA-3notablyblocksPU.1andIL-7Rαexpression,andPU.1reducesexpressionofHES-1andc-Myb.Afirst-draftassemblyoftheregulatorytargetsofthesetwofactorsispresentedasaprovisionalgenenetwork.ThetargetgenesidentifiedhereprovideinsightintothebasisoftheeffectsofGATA-3orPU.1overexpressionandintotheregulatorychangesthatdistinguishthedevelopmentaltimewindowsfortheseeffects.

【 授权许可】

Unknown