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Journal of Virology, May 2002, p. 4364-4369, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4364-4369.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Common Retroviral Insertion Locus Dsi1 Maps 30 Kilobases Upstream of the P1 Promoter of the Murine Runx3/Cbfa3/Aml2 Gene

Monica Stewart,* Nancy MacKay, Ewan R. Cameron, and James C. Neil

Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow G61 1QH, United Kingdom

Received 3 December 2001/ Accepted 4 February 2002

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.

* Corresponding author. Mailing address: Molecular Oncology Laboratory, Institute of Comparative Medicine, Department of Veterinary Pathology, University of Glasgow Veterinary School, Bearsden Rd., Glasgow G61 1QH, United Kingdom. Phone: 44 141 330 5608. Fax: 44 141 330 6467. E-mail: m.stewart{at}vet.gla.ac.uk.

Journal of Virology, May 2002, p. 4364-4369, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4364-4369.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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