Altered 3D chromatin structure permits inversional recombination at the IgH locus

We report that in the absence of intergenic control region 1 (IGCR1), a regulatory sequence that specifies the RAG scanning domain on WT IgH alleles, VH and DH gene segments can recombine with each other by both deletion and inversion of intervening DNA. Overall design: Analysis of VH and DH utilization in different Pro-B cell lines. Immunoglobulin heavy chain (IgH) locus comprises variable (V), diversity (D) and joining (J) gene segments. Both DQ52 and DSP2 belong to D gene segments. Our main purpose was to identify deletional (and inversional) recombination at the WT or IGCR1 deficient IgH locus. Therefore, we used deep sequencing method to test our hypothesis with DQ52 as bait and DSP as bait. DQ52 as bait refers to DQ52-J or DQ52-VH81X (the first functional proximal VH gene segment) recombination. DSP as bait refers to DSP-J or DSP-VH81X recombination.