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

[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.

[学科分类] 生物科学（综合）

[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