| First Author | Puget N | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 35 |
| Issue | 13 | Pages | 2231-41 |
| PubMed ID | 25896912 | Mgi Jnum | J:266641 |
| Mgi Id | MGI:6248294 | Doi | 10.1128/MCB.00294-15 |
| Citation | Puget N, et al. (2015) Complete cis Exclusion upon Duplication of the Emu Enhancer at the Immunoglobulin Heavy Chain Locus. Mol Cell Biol 35(13):2231-41 |
| abstractText | Developing lymphocytes somatically diversify their antigen-receptor loci through V(D)J recombination. The process is associated with allelic exclusion, which results in monoallelic expression of an antigen receptor locus. Various cis-regulatory elements control V(D)J recombination in a developmentally regulated manner, but their role in allelic exclusion is still unclear. At the immunoglobulin heavy chain locus (IgH), the Emu enhancer plays a critical role in V(D)J recombination. We generated a mouse line with a replacement mutation in the constant region of the locus that duplicates the Emu enhancer and allows premature expression of the gamma3 heavy chain. Strikingly, IgM expression was completely and specifically excluded in cis from the mutant allele. This cis exclusion recapitulated the main features of allelic exclusion, including differential exclusion of variable genes. Notably, sense and antisense transcription within the distal variable domain and distal V(H)-DJ(H) recombination were inhibited. cis exclusion was established and stably maintained despite an active endogenous Emu enhancer. The data reveal the importance of the dynamic, developmental stage-dependent interplay between IgH locus enhancers and signaling in the induction and maintenance of allelic exclusion. |
