Large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination at the IgH locus in a cell-type specific manner

In this study, we compare the chromatin structure of the Ig heavy (IgH) chain locus (performing MNase digestion) in three murine cell types rendered recombinationally inactive by loss of a RAG recombinase: (i) RAG2-/- Pro-B cell lines, where the entire IgH locus is poised and available for recombination, (ii) RAG1-/- Pro-T cell lines, lymphoid cells where the IgH locus is partly open but the V region does not rearrange, (iii) recombinationally inactive RAG2-/- mouse embryonic fibroblasts (MEFs), where the entire IgH locus is in a closed conformation and unavailable for rearrangement. Our findings suggest that developmentally-regulated changes in nucleosome location and occupancy play a fundamental role in regulating V(D)J recombination, by creating and controlling the accessibility of recombination signal sequences. Comparison of nucleosome mapping at the IgH locus between Rag-deficient proB, MEFs and proT cells. Two independent biological replicates were assessed for each cell type.