Flanking nuclear matrix attachment regions synergize with the T cell receptor delta 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, Igkappa, and T cell receptor (TCR) beta 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 delta gene. Two of these are located within the Jdelta3-Cdelta intron, flanking the core TCR delta enhancer (Edelta) 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 Ddelta1 and Ddelta2. We have previously used a transgenic minilocus V(D)J recombination reporter to establish that Edelta 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 Edelta-associated MARs function synergistically with the core Edelta to promote V(D)J recombination in this system, as they are required for enhancer-dependent transgene rearrangement in single-copy transgene integrants.
Zhong
X P
XP
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Carabaña
J
J
Krangel
M S
MS
D000818:Animals; D001483:Base Sequence; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015530:Nuclear Matrix / Q000235:genetics* / Q000276:immunology*; D010957:Plasmids / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D011995:Recombination, Genetic / Q000502:physiology*; D045567:VDJ Recombinases
D016692:Receptors, Antigen, T-Cell, gamma-delta; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases