International Immunology, Vol. 13, No. 11, 1405-1414,
November 2001
© 2001 Japanese Society for Immunology
Limited effect of chromatin remodeling on Dß-to-Jß recombination in CD4+CD8+ thymocyte: implications for a new aspect in the regulation of TCR ß gene recombination
1 Department of Immunology, Tokai University School of Medicine, Bouseidai, Isehara, Kanagawa 259-1193, Japan
2 Core Research for Evolution Science and Technology (CREST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
3 Center of Animal Research and Development, Kumamoto University, 4-21-1 Kuhonji, Kumamoto 862-0976, Japan
4 Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Shogoin, Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Correspondence to: Y. Shinkai and S. Habu
We have generated mutant mice in which TCR ß chain enhancer (Eß) was replaced with the TCR 
chain enhancer (E). Using this mouse model, we analyzed (i) recombination status of the TCR ß chain genes after functional V(D)J rearrangements occurred in the first allele during double-negative (DN)-to-double-positive (DP) transition and (ii) involvement of Eß for the expression of rearranged TCR ß chain genes. Our data show that E substituted for Eß function to express a similar extent of TCR ß chains exactly at the same time as did Eß (CD25+CD44– DN stage), although the proportion of TCR ß+ cells at this stage was low in mutant mice. At the DP stage, germline transcription and histone acetylation of Dß–Jß loci were detectable at a high degree in both mutant and wild-type mice. However, DP cells in mutant mice retained the germline Dß–Jß configuration at a higher frequency than that of wild-type mice, whereas both DP cells expressed TCR ß chains to a similar extent. These data suggest that chromatin opening has a limited impact on Dß-to-Jß recombination at the DP stage and that E is functionally equivalent to Eß in promoting expression of functionally rearranged TCR ß chain genes through DN-to-DP transition.
Keywords: allelic exclusion, germline transcription, histone acetylation, rearrangement, TCR enhancer (E), TCR ß enhancer (Eß)
Transmitting editor: T. Watanabe
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