Accessibility and the developmental regulation of V(D)J recombination.
Antigen receptor genes are assembled from their component gene segments by a highly regulated series of site-specific DNA recombination reactions known as V(D)J recombination. Proteins encoded by the RAG1 and RAG2 genes are responsible for the recognition and double-stranded cleavage of a highly conserved DNA sequence flanking all rearranging gene segments. It remains uncertain how this common lymphoid recombinase is targeted to distinct loci in developing B and T cells and to specific loci at successive stages of lymphocyte development. This review considers evidence that DNA sequences which regulate the transcription of antigen receptor genes also regulate the recombination reaction by determining the accessibility of individual loci to the V(D)J recombinase.
Schlissel
M S
MS
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stanhope-Baker
P
P
D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004254:DNA Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D015321:Gene Rearrangement; D018390:Gene Targeting; D018398:Homeodomain Proteins; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009687:Nuclear Proteins; D011946:Receptors, Antigen / Q000235:genetics*; D011995:Recombination, Genetic; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D011946:Receptors, Antigen; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases