An inducible cell model for studies of V(D)J recombinational control.
Antigen receptor gene assembly is controlled by enhancer-directed changes in the accessibility of chromosomal gene segments to V(D)J recombinase. To dissect mechanisms that regulate rearrangement efficiencies, we developed a cell system (TDR19) in which recombination activating gene (RAG) expression is repressed by tetracycline. Under conditions of RAG repression, recombination substrates were consistently integrated into the TDR19 genome in an unrearranged form. Subsequent rearrangement of chromosomal substrates containing a transcriptional enhancer correlated inversely with tetracycline concentrations. Together, these features underscore the utility of TDR19 as a cell model for defining the molecular determinants of V(D)J recombinational accessibility.
Sikes
M L
ML
Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232, USA.
Oltz
E M
EM
D002460:Cell Line; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D016654:Genes, RAG-1 / Q000235:genetics*; D008954:Models, Biological; D011995:Recombination, Genetic; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; C064655:V(D)J recombination activating protein 2; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases