Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1

被引:133
作者
Kwon, J
Imbalzano, AN
Matthews, A
Oettinger, MA [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[3] Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA
关键词
D O I
10.1016/S1097-2765(00)80297-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, Mere we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DNA-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 call be modulated by controlling substrate accessibility and cleavage at the level of an individual nucleosome.
引用
收藏
页码:829 / 839
页数:11
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