DEVELOPMENTAL REGULATION OF V(D)J RECOMBINATION AT THE TCR ALPHA DELTA LOCUS/

The T-cell receptor (TCR) alpha/delta locus includes a large number of V, D, J and C gene segments that are used to produce functional TCR d elta and TCR alpha chains expressed by distinct subsets of T lymphocyt es. V(D)J recombination events within the locus are regulated as a fun ction of developmental stage and cell, lineage during T-lymphocyte dif ferentiation in the thymus, The process of V(D)J recombination is regu lated by cis-acting elements that modulate the accessibility of chromo somal substrates to the recombinase. Here we evaluate how the assembly oi transcription factor complexes onto enhancers, promoters and other regulatory elements within the TCR alpha/delta locus imparts developm ental control to VDJ delta and VJ alpha rearrangement events. Furtherm ore, we develop the notion that within a complex locus such as the TCR alpha/delta locus, highly localized and region-specific control is li kely to require an interplay between positive regulatory elements and blocking or boundary elements that restrict the influence of the posit ive elements to defined regions of the locus.