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.
Hernández-Munain
C
C
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Sleckman
B P
BP
Krangel
M S
MS
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