The T-Cell receptor ß variable gene promoter is required for efficient Vß rearrangement but not allelic exclusion

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Title
The T-Cell receptor ß variable gene promoter is required for efficient Vß rearrangement but not allelic exclusion
Author(s)
Chun Jeih Ryu; B B Haines; H R Lee; Yun Hee Kang; D D Draganov; M H Lee; C E Whitehurst; Hyo Jeong Hong; J Chen
Bibliographic Citation
Molecular and Cellular Biology, vol. 24, no. 16, pp. 7015-7023
Publication Year
2004
Abstract
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.
ISSN
0270-7306
Publisher
Amer Soc Microb
DOI
http://dx.doi.org/10.1128/MCB.24.16.7015-7023.2004
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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