The common retroviral insertion locus Dsi1 maps 30 kilobases upstream of the P1 promoter of the murine Runx3/Cbfa3/Aml2 gene.
The Dsi1 locus was identified as a common integration site for Moloney murine leukemia virus (MLV) in rat thymic lymphomas, but previous efforts to identify a gene affected by these insertions were unsuccessful. We considered the Runx3 gene a potential candidate on the basis of genetic mapping which showed that Dsi1 and Runx3 are closely linked on mouse chromosome 4 and the precedent of the related Runx2 gene, which emerged recently as a Myc-collaborating gene activated by retroviral insertion in thymic lymphomas of CD2-MYC mice. We now report the physical mapping of the Dsi1 locus to a site 30 kb upstream of the distal (P1) promoter of the murine Runx3 gene. Comparison with the syntenic region of human chromosome 1 shows that the next gene is over 250 kb 5' to Runx3, suggesting that Runx3 may be the primary target of retroviral insertions at Dsi1. Screening of CD2-MYC lymphomas for rearrangements at Dsi1 revealed a tumor cell line harboring an MLV provirus at this locus, in the orientation opposite that of Runx3. Proviral insertion was associated with very high levels of expression of Runx3, with a preponderance of transcripts arising at the P1 promoter. These results confirm that Runx3 is a target of retroviral insertions at Dsi1 and indicate that Runx3 can act as an alternative to Runx2 as a Myc-collaborating gene in thymic lymphoma.
Stewart
Monica
M
Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow G61 1QH, United Kingdom. m.stewart@vet.gla.ac.uk
MacKay
Nancy
N
Cameron
Ewan R
ER
Neil
James C
JC
D000818:Animals; D027042:Chromosomes, Artificial, P1 Bacteriophage; D050677:Core Binding Factor Alpha 3 Subunit; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000235:genetics*; D015723:Gene Library; D016259:Genes, myc; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000235:genetics*; D020161:Physical Chromosome Mapping; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics*; D012192:Retroviridae Infections / Q000235:genetics / Q000821:virology; D013953:Thymus Neoplasms / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology; D016662:Virus Integration / Q000235:genetics*
D050677:Core Binding Factor Alpha 3 Subunit; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; C493730:Runx3 protein, mouse; D014157:Transcription Factors