A developmental switch from TCRδ enhancer to TCRα enhancer function during thymocyte maturation

V(D)J recombination and transcription within the TCR alpha/delta locus are regulated by three characterized cia-acting elements: the TCR delta enhancer (E delta), TCR alpha enhancer (E alpha), and T early alpha (TEA) promoter. Analysis of enhancer and promoter occupancy and function in developing thymocytes in vivo indicates E delta and E alpha to be developmental-stage-specific enhancers, with E delta "on" and E alpha "off" in double-negative III thymocytes and E delta "off" and E alpha "on" in double-positive thymocytes. E delta downregulation reflects a loss of occupancy. Surprisingly, E alpha and TEA are extensively occupied even prior to activation. TCR delta downregulation in double-positive thymocytes depends on two events, E delta inactivation and removal of TCR delta from the influence of E alpha by chromosomal excision.