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Molecular and Cellular Biology, April 1999, p. 2601-2612, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Distinct Factors Regulate the Murine RAG-2 Promoter in B- and T-Cell Lines

Josh Lauring and Mark S. Schlissel*

Department of Medicine, Department of Oncology, and Department of Molecular Biology and Genetics, Graduate Program in Biochemistry, Cellular, and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Received 13 August 1998/Returned for modification 22 September 1998/Accepted 7 December 1998

The recombination activating genes RAG-1 and RAG-2 are expressed in a lymphoid-cell-specific and developmentally regulated fashion. To understand the transcriptional basis for this regulation, we have cloned and characterized the murine RAG-2 promoter. The promoter was lymphoid cell specific, showing activity in various B- and T-cell lines but little activity in nonlymphoid cells. To our surprise, however, the promoter was regulated differently in B and T cells. Using nuclear extracts from B-cell lines, we found that the B-cell-specific transcription factor BSAP (Pax-5) could bind to a conserved sequence critical for promoter activity. BSAP activated the promoter in transfected cells, and the BSAP site was occupied in a tissue-specific manner in vivo. An overlapping DNA sequence binding to a distinct factor was necessary for promoter activity in T cells. Full promoter activity in T cells was also dependent on a more distal DNA sequence whose disruption had no effect on B-cell activity. The unexpected finding that a B-cell-specific factor regulates the RAG-2 promoter may explain some of the recently observed differences in the regulation of RAG transcription between B and T cells.

* Corresponding author. Mailing address: Department of Medicine, Department of Oncology, and Department of Molecular Biology and Genetics, Graduate Program in Biochemistry, Cellular, and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. Phone: (410) 502-6453. Fax: (410) 955-0964. E-mail: mss{at}welchlink.welch.jhu.edu.

Molecular and Cellular Biology, April 1999, p. 2601-2612, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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