First Author | Ryu CJ | Year | 2004 |
Journal | Mol Cell Biol | Volume | 24 |
Issue | 16 | Pages | 7015-23 |
PubMed ID | 15282302 | Mgi Jnum | J:92288 |
Mgi Id | MGI:3052302 | Doi | 10.1128/MCB.24.16.7015-7023.2004 |
Citation | Ryu CJ, et al. (2004) The T-cell receptor beta variable gene promoter is required for efficient V beta rearrangement but not allelic exclusion. Mol Cell Biol 24(16):7015-23 |
abstractText | 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 V beta 13 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 V beta 13, but not the flanking V beta gene segments, were significantly inhibited. In P13(R/R) mice, inhibition of V beta 13 rearrangement was less severe and was not associated with any apparent reduction in V beta 13 cleavage. Expression of a T-cell receptor (TCR) transgene blocked cleavages at the normal V beta 13-recombination signal sequence junction and V beta 13 coding joint formation of both wild-type and mutant V beta 13 alleles. However, a low level of aberrant V beta 13 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 V beta gene segment. Although the promoter is dispensable for allelic exclusion, it appears to suppress aberrant V beta cleavages during allelic exclusion. |