Enhancer-instructed epigenetic landscape and chromatin compartmentalization dictate a primary antibody repertoire protective against specific bacterial pathogens.

ABSTRACT: Antigen receptor loci are organized into variable (V), diversity (D) and joining (J) gene segments that rearrange to generate antigen receptor repertoires. Here, we identified an enhancer (E34) in the murine immunoglobulin kappa (Igk) locus that instructed rearrangement of V_κ genes located in a sub-topologically associating domain, including a V_κ gene encoding for antibodies targeting bacterial phosphorylcholine. We show that E34 instructs the nuclear repositioning of the E34 sub-topologically associating domain from a recombination-repressive compartment to a recombination-permissive compartment that is marked by equivalent activating histone modifications. Finally, we found that E34-instructed V_κ-J_κ rearrangement was essential to combat Strepto

SUBMITTER: Barajas-Mora EM 

PROVIDER: S-EPMC10917333 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature