Limited effect of chromatin remodeling on D-beta-to-J(beta) recombination in CD4(+)CD8(+) thymocyte: implications for a new aspect in the regulation of TCR beta gene recombination
M. Senoo et al., Limited effect of chromatin remodeling on D-beta-to-J(beta) recombination in CD4(+)CD8(+) thymocyte: implications for a new aspect in the regulation of TCR beta gene recombination, INT IMMUNOL, 13(11), 2001, pp. 1405-1414
We have generated mutant mice in which TCR beta chain enhancer (E-beta) was
replaced with the TCR beta chain enhancer (E-alpha). Using this mouse mode
l, we analyzed (1) recombination status of the TCR beta chain genes after f
unctional V(D)J rearrangements occurred in the first allele during double-n
egative (DN)-to-double-positive (DP) transition and (ii) involvement of E-b
eta for the expression of rearranged TCR beta chain genes. Our data show th
at E-alpha substituted for E-beta function to express a similar extent of T
CR beta chains exactly at the same time as did E-beta (CD25(+)CD44(-) DN st
age), although the proportion of TCR beta (+) cells at this stage was low i
n mutant mice. At the DP stage, germline transcription and histone acetylat
ion of D-beta-J(beta) loci were detectable at a high degree in both mutant
and wild-type mice. However, DP cells in mutant mice retained the germline
D-beta-J(beta) configuration at a higher frequency than that of wild-type m
ice, whereas both DP cells expressed TCR beta chains to a similar extent. T
hese data suggest that chromatin opening has a limited impact on D-beta-to-
J(beta) recombination at the DP stage and that E-alpha is functionally equi
valent to E-beta in promoting expression of functionally rearranged TCR bet
a chain genes through DN-to-DP transition.