Identification of a third evolutionarily conserved gene within the RAG locus and its RAG1-dependent and -independent regulation.
Recombination-activating gene (RAG)1 and RAG2 encode T and B lymphocyte-specific endonucleases indispensable for rearrangements of antigen-receptor gene segments but also capable of causing deleterious chromosome rearrangements. The mechanisms regulating RAG expression and repression are not clear. Here we identify NWC, a third evolutionarily conserved gene within the RAG locus, and show that it is ubiquitously expressed, with the notable exception of RAG-nonexpressing immature and mature T and B lymphocytes because in lymphocytes it is regulated by the RAG1 promoter and transcribed as RAG1-NWC hybrid mRNA molecules. We also show that in all other cells NWC is controlled by the RAG2 intragenic promoter, which in immature and mature T and B lymphocytes is silent. The possible implications of these findings for understanding the activation and inactivation of RAG genes in lymphocytes and their repression in other cells are discussed.
Cebrat
Malgorzata
M
Department of Tumor Immunology, Laboratory of Transgenesis and Lymphocyte Biology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Miazek
Arkadiusz
A
Kisielow
Pawel
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D004285:Dogs; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000276:immunology*; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein