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 cia-acting elements: the TCR delta enhance r (E delta), TCR alpha enhancer (E alpha), and T early alpha (TEA) promoter . Analysis of enhancer and promoter occupancy and function in developing th ymocytes in vivo indicates E delta and E alpha to be developmental-stage-sp ecific enhancers, with E delta "on" and E alpha "off" in double-negative II I thymocytes and E delta "off" and E alpha "on" in double-positive thymocyt es. E delta downregulation reflects a loss of occupancy. Surprisingly, E al pha and TEA are extensively occupied even prior to activation. TCR delta do wnregulation in double-positive thymocytes depends on two events, E delta i nactivation and removal of TCR delta from the influence of E alpha by chrom osomal excision.