title: E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment.
abstract: The E2A transcription factors promote the development of thymus-seeding cells, but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. Here, we showed that E2A proteins were required to promote T-lymphocyte commitment from DN2 thymocytes and to extinguish their potential for alternative fates. E2A proteins functioned in DN2 cells to limit expression of Gata3, which encodes an essential T-lymphocyte transcription factor whose ectopic expression can arrest T-cell differentiation. Genetic, or small interfering RNA-mediated, reduction of Gata3 rescued T-cell differentiation in the absence of E2A and restricted the development of alternative lineages by limiting the expanded self-renewal potential in E2A−/− DN2 cells. Our data support a novel paradigm in lymphocyte lineage commitment in which the E2A proteins are necessary to limit the expression of an essential lineage specification and commitment factor to restrain self-renewal and to prevent an arrest in differentiation.
authors.affiliation: Committees on Cancer Biology and. Immunology, Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Tiffany
authors.initials: T
authors.lastname: Carr
authors.forename: Kevin
authors.initials: K
authors.lastname: Ramirez
authors.forename: Stephanie
authors.initials: S
authors.lastname: McGregor
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Kee
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D060168:Thymocytes / Q000378:metabolism / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C075668:Tcf3 protein, mouse