title: Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs.
abstract: The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell-specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte-specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte-specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell-regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell-specific transcriptional activity.
authors.forename: Sakie
authors.initials: S
authors.lastname: Ohmura
authors.forename: Seiya
authors.initials: S
authors.lastname: Mizuno
authors.forename: Hisashi
authors.initials: H
authors.lastname: Oishi
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Ku
authors.forename: Mary
authors.initials: M
authors.lastname: Hermann
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hosoya
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002454:Cell Differentiation; D019070:Cell Lineage; D004742:Enhancer Elements, Genetic; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D011485:Protein Binding; D060168:Thymocytes / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse