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Molecular and Cellular Biology, August 2004, p. 7015-7023, Vol. 24, No. 16
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.16.7015-7023.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The T-Cell Receptor ß Variable Gene Promoter Is Required for Efficient Vß Rearrangement but Not Allelic Exclusion

Chun Jeih Ryu,^1,2 Brian B. Haines,¹ Hye Ran Lee,^1, Yun Hee Kang,² Dobrin D. Draganov,¹ Minhui Lee,¹ Charles E. Whitehurst,¹ Hyo Jeong Hong,² and Jianzhu Chen^1*

Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139,¹ Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejon 305-600, Korea²

Received 4 February 2004/ Returned for modification 8 March 2004/ Accepted 19 May 2004

To investigate the role of promoters in regulating variable gene rearrangement and allelic exclusion, we constructed mutant mice in which a 1.2-kb region of the Vß13 promoter was either deleted (P13^–/–) or replaced with the simian virus 40 minimal promoter plus five copies of Gal4 DNA sequences (P13^R/R). In P13^–/– mice, cleavage, rearrangement, and transcription of Vß13, but not the flanking Vß gene segments, were significantly inhibited. In P13^R/R mice, inhibition of Vß13 rearrangement was less severe and was not associated with any apparent reduction in Vß13 cleavage. Expression of a T-cell receptor (TCR) transgene blocked cleavages at the normal Vß13-recombination signal sequence junction and Vß13 coding joint formation of both wild-type and mutant Vß13 alleles. However, a low level of aberrant Vß13 cleavage was consistently detected, especially in TCR transgenic P13^R/R mice. These findings suggest that the variable gene promoter is required for promoting local recombination accessibility of the associated Vß gene segment. Although the promoter is dispensable for allelic exclusion, it appears to suppress aberrant Vß cleavages during allelic exclusion.

Present address: Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Ilsan-gu, Goyang 411-706, South Korea.

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