Flanking nuclear matrix attachment regions synergize with the T cell receptor δ enhancer to promote V(D)J recombination

Previous studies have identified nuclear matrix attachment regions (MARs) that are closely associated with transcriptional enhancers in the IgH, Igκ, and T cell receptor (TCR) β loci, but have yielded conflicting information regarding their functional significance. In this report, a combination of in vitro and in situ mapping approaches was used to localize three MARs associated with the human TCR δ gene. Two of these are located within the Jδ3–Cδ intron, flanking the core TCR δ enhancer (Eδ) both 5′ and 3′ in a fashion reminiscent of the Ig heavy chain intronic enhancer-associated MARs. The third is located about 20 kb upstream, tightly linked to Dδ1 and Dδ2. We have previously used a transgenic minilocus V(D)J recombination reporter to establish that Eδ functions as a developmental regulator of V(D)J recombination, and that it does so by modulating substrate accessibility to the V(D)J recombinase. We show here that the Eδ-associated MARs function synergistically with the core Eδ to promote V(D)J recombination in this system, as they are required for enhancer-dependent transgene rearrangement in single-copy transgene integrants.