| First Author | Wang X | Year | 2008 |
| Journal | Nat Immunol | Volume | 9 |
| Issue | 7 | Pages | 794-801 |
| PubMed ID | 18500346 | Mgi Jnum | J:137883 |
| Mgi Id | MGI:3803090 | Doi | 10.1038/ni.1614 |
| Citation | Wang X, et al. (2008) Regulation of Tcrb recombination ordering by c-Fos-dependent RAG deposition. Nat Immunol 9(7):794-801 |
| abstractText | Antigen receptor variable-(diversity)-joining (V(D)J) recombination at the locus encoding the T cell antigen receptor-beta (Tcrb) is ordered, with D(beta)-to-J(beta) assembly preceding V(beta)-to-DJ(beta) joining. The molecular mechanism underlying this 'preferred' order of rearrangement remains unclear. Here we show that the D(beta) 23-base pair recombination signal sequence (D(beta) 23-RSS) contains a specific AP-1 transcription factor-binding site bound by AP-1 and its component c-Fos expressed at a specific stage. Cell-based recombination assays suggested that c-Fos interacted directly with the RAG recombinase and enhanced its deposition to D(beta) 23-RSSs, thus conferring the priority of DJ(beta) recombination. Loss of c-Fos decreased Tcrb recombination efficiency and disrupted recombination ordering in vivo. Our results show an unexpected function for c-Fos as a direct regulator of Tcrb recombination, rather than its usual function as a transcription regulator, and provide new insight into the mechanisms of recombination ordering. |
