title: Regulation of GATA-3 expression during CD4 lineage differentiation.
abstract: GATA-3 is necessary for the development of MHC class II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TCR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches, we show that GATA-3 upregulation during thymocyte-positive selection is the result of additive inputs from the Ras/MAPK and calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double-positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation.
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Idoia
authors.initials: I
authors.lastname: Gimferrer
authors.forename: Taishan
authors.initials: T
authors.lastname: Hu
authors.forename: Amie
authors.initials: A
authors.lastname: Simmons
authors.forename: Chi
authors.initials: C
authors.lastname: Wang
authors.forename: Abdallah
authors.initials: A
authors.lastname: Souabni
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Bender
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hernandez-Hoyos
authors.forename: José
authors.initials: J
authors.lastname: Alberola-Ila
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019703:Calcineurin / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000502:physiology; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D055879:Gene Knock-In Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020598:Proto-Oncogene Proteins c-myb / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D020598:Proto-Oncogene Proteins c-myb; D014157:Transcription Factors; C484225:ZBTB7B protein, human; D019703:Calcineurin; D018631:ras Proteins