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

Jongbum Kwon, Anthony N. Imbalzano, Adam Matthews, Marjorie A. Oettinger

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

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 languageEnglish
Pages (from-to)829-839
Number of pages11
JournalMolecular Cell
Volume2
Issue number6
DOIs
StatePublished - Dec 1998

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