An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36869028.
- Also identified by DOI 10.1038/s41467-023-36414-2 and PMC identifier 9984487.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The mouse Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of distal V<sub>H</sub> enhancers (E<sub>VH</sub>s) that collaborate to configure the locus. E<sub>VH</sub>s engage in a network of long-range interactions that interconnect the subTADs and the recombination center at the D<sub>H</sub>J<sub>H</sub> gene cluster. Deletion of E<sub>VH</sub>1 reduces V gene rearrangement in its vicinity and alters discrete chromatin loops and higher order locus conformation. Reduction in the rearrangement of the V<sub>H</sub>11 gene used in anti-PtC responses is a likely cause of the observed reduced splenic B1 B cell compartment. E<sub>VH</sub>1 appears to block long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant V<sub>H</sub> genes to the recombination center. E<sub>VH</sub>1 is a critical architectural and regulatory element that coordinates chromatin conformational states that favor V(D)J rearrangement.
Medical subject headings
- B-Lymphocytes
- Regulatory Sequences, Nucleic Acid
- Immunoglobulin Heavy Chains