TY - JOUR
T1 - Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1
AU - Kwon, Jongbum
AU - Imbalzano, Anthony N.
AU - Matthews, Adam
AU - Oettinger, Marjorie A.
N1 - 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.).
PY - 1998/12
Y1 - 1998/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032239155&partnerID=8YFLogxK
U2 - 10.1016/S1097-2765(00)80297-X
DO - 10.1016/S1097-2765(00)80297-X
M3 - Article
C2 - 9885570
AN - SCOPUS:0032239155
SN - 1097-2765
VL - 2
SP - 829
EP - 839
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -