AI Article Synopsis

  • The study focuses on the structural changes in immunoglobulin heavy-chain (Igh) loci that create diverse antibody repertoires, revealing the complexity of chromosomal interactions involved.
  • Using a technique called tiled Capture Hi-C, researchers mapped chromatin interactions in the Igh locus of progenitor B cells, showing how the locus forms subdomains and flexible loops for gene recombination.
  • They found that the unique structures of the Igh locus, along with interactions between different immunoglobulin loci and developmental factors, suggest a coordinated network that influences B cell development and antibody diversity.

Article Abstract

To produce a diverse antibody repertoire, immunoglobulin heavy-chain (Igh) loci undergo large-scale alterations in structure to facilitate juxtaposition and recombination of spatially separated variable (V), diversity (D), and joining (J) genes. These chromosomal alterations are poorly understood. Uncovering their patterns shows how chromosome dynamics underpins antibody diversity. Using tiled Capture Hi-C, we produce a comprehensive map of chromatin interactions throughout the 2.8-Mb Igh locus in progenitor B cells. We find that the Igh locus folds into semi-rigid subdomains and undergoes flexible looping of the V genes to its 3' end, reconciling two views of locus organization. Deconvolution of single Igh locus conformations using polymer simulations identifies thousands of different structures. This heterogeneity may underpin the diversity of V(D)J recombination events. All three immunoglobulin loci also participate in a highly specific, developmentally regulated network of interchromosomal interactions with genes encoding B cell-lineage factors. This suggests a model of interchromosomal coordination of B cell development.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10548092PMC
http://dx.doi.org/10.1016/j.celrep.2023.113074DOI Listing

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