The T-cell receptor beta variable gene promoter is required for efficient V beta rearrangement but not allelic exclusion.
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.
Ryu
Chun Jeih
CJ
Center for Cancer Research and Department of Biology, Massachusetts Institute for Technology, Cambridge, MA 02139, USA.
Haines
Brian B
BB
Lee
Hye Ran
HR
Kang
Yun Hee
YH
Draganov
Dobrin D
DD
Lee
Minhui
M
Whitehurst
Charles E
CE
Hong
Hyo Jeong
HJ
Chen
Jianzhu
J
D000483:Alleles; D000818:Animals; D005786:Gene Expression Regulation; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019674:Genes, T-Cell Receptor beta; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D019076:Transgenes
D011948:Receptors, Antigen, T-Cell