Abstract
B and T cell receptor gene assembly by V(D)J recombination is tightly regulated during lymphoid development. The mechanisms involved in this regulation are poorly understood. Here we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DMA-binding protein, stimulates V(D)J cleavage of nucleosomal templates. This HMG1 stimulation is differentially affected by the rotational or translational positioning of the recombination signal sequence on the histone octamer, with cleavage of the 12 bp spacer RSS showing sensitivity to rotational position and the 23 bp spacer RSS affected by its displacement from the dyad. These results suggest that V(D)J recombination can be modulated by controlling substrate accessibility and cleavage at the level of an individual nucleosome.
| Original language | English |
|---|---|
| Pages (from-to) | 829-839 |
| Number of pages | 11 |
| Journal | Molecular Cell |
| Volume | 2 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1998 |
Bibliographical note
Funding Information:We thank Reid Johnson and Tanya Paull for the gift of HMG1, Robert Kingston, Gavin Schnitzler, Said Sif, and members of the Oettinger lab for helpful discussions, and Robert Kingston and Cynthia Mundy for critical reading of the manuscript. This work was supported by National Institutes of Health grant GM58026, the Leukemia Society Scholars Program, the Pew Scholars Program, and Hoechst AG (to M. A. O.) and GM48405 (to R. E. K.).