| First Author | Vettermann C | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 1 | Pages | e0113824 |
| PubMed ID | 25559567 | Mgi Jnum | J:225367 |
| Mgi Id | MGI:5693189 | Doi | 10.1371/journal.pone.0113824 |
| Citation | Vettermann C, et al. (2015) The proximal J kappa germline-transcript promoter facilitates receptor editing through control of ordered recombination. PLoS One 10(1):e0113824 |
| abstractText | V(D)J recombination creates antibody light chain diversity by joining a Vkappa gene segment with one of four Jkappa segments. Two Jkappa germline-transcript (GT) promoters control Vkappa-Jkappa joining, but the mechanisms that govern Jkappa choice are unclear. Here, we show in gene-targeted mice that the proximal GT promoter helps targeting rearrangements to Jkappa1 by preventing premature DNA breaks at Jkappa2. Consequently, cells lacking the proximal GT promoter show a biased utilization of downstream Jkappa segments, resulting in a diminished potential for receptor editing. Surprisingly, the proximal--in contrast to the distal--GT promoter is transcriptionally inactive prior to Igkappa recombination, indicating that its role in Jkappa choice is independent of classical promoter function. Removal of the proximal GT promoter increases H3K4me3 levels at Jkappa segments, suggesting that this promoter could act as a suppressor of recombination by limiting chromatin accessibility to RAG. Our findings identify the first cis-element critical for Jkappa choice and demonstrate that ordered Igkappa recombination facilitates receptor editing. |
