Altered 3D chromatin structure permits inversional recombination at the <i>IgH</i> locus.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32851160.
- Also identified by DOI 10.1126/sciadv.aaz8850 and PMC identifier 7428332.
- Licence recorded as CC BY-NC.
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Abstract
Immunoglobulin heavy chain (<i>IgH</i>) genes are assembled by two sequential DNA rearrangement events that are initiated by recombination activating gene products (RAG) 1 and 2. Diversity (D<sub>H</sub>) gene segments rearrange first, followed by variable (V<sub>H</sub>) gene rearrangements. Here, we provide evidence that each rearrangement step is guided by different rules of engagement between rearranging gene segments. D<sub>H</sub> gene segments, which recombine by deletion of intervening DNA, must be located within a RAG1/2 scanning domain for efficient recombination. In the absence of intergenic control region 1, a regulatory sequence that delineates the RAG scanning domain on wild-type <i>IgH</i> alleles, V<sub>H</sub> and D<sub>H</sub> gene segments can recombine with each other by both deletion and inversion of intervening DNA. We propose that V<sub>H</sub> gene segments find their targets by distinct mechanisms from those that apply to D<sub>H</sub> gene segments. These distinctions may underlie differential allelic choice associated with each step of <i>IgH</i> gene assembly.