A developmental switch from TCR delta enhancer to TCR alpha enhancer function during thymocyte maturation.
V(D)J recombination and transcription within the TCR alpha/delta locus are regulated by three characterized cis-acting elements: the TCR delta enhancer (Edelta), TCR alpha enhancer (Ealpha), and T early alpha (TEA) promoter. Analysis of enhancer and promoter occupancy and function in developing thymocytes in vivo indicates Edelta and Ealpha to be developmental-stage-specific enhancers, with Edelta "on" and Ealpha "off" in double-negative III thymocytes and Edelta "off" and Ealpha "on" in double-positive thymocytes. Edelta downregulation reflects a loss of occupancy. Surprisingly, Ealpha and TEA are extensively occupied even prior to activation. TCR delta downregulation in double-positive thymocytes depends on two events, Edelta inactivation and removal of TCR delta from the influence of Ealpha by chromosomal excision.
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
C
C
Hernández-Munain
B P
BP
Sleckman
M S
MS
Krangel
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D018983:DNA Footprinting; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D005812:Genes, Switch / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology*; D019676:Genes, T-Cell Receptor delta / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology; D011995:Recombination, Genetic; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism