| First Author | Stadhouders R | Year | 2014 |
| Journal | PLoS Biol | Volume | 12 |
| Issue | 2 | Pages | e1001791 |
| PubMed ID | 24558349 | Mgi Jnum | J:208412 |
| Mgi Id | MGI:5563273 | Doi | 10.1371/journal.pbio.1001791 |
| Citation | Stadhouders R, et al. (2014) Pre-B cell receptor signaling induces immunoglobulin kappa locus accessibility by functional redistribution of enhancer-mediated chromatin interactions. PLoS Biol 12(2):e1001791 |
| abstractText | During B cell development, the precursor B cell receptor (pre-BCR) checkpoint is thought to increase immunoglobulin kappa light chain (Igkappa) locus accessibility to the V(D)J recombinase. Accordingly, pre-B cells lacking the pre-BCR signaling molecules Btk or Slp65 showed reduced germline V(kappa) transcription. To investigate whether pre-BCR signaling modulates V(kappa) accessibility through enhancer-mediated Igkappa locus topology, we performed chromosome conformation capture and sequencing analyses. These revealed that already in pro-B cells the kappa enhancers robustly interact with the approximately 3.2 Mb V(kappa) region and its flanking sequences. Analyses in wild-type, Btk, and Slp65 single- and double-deficient pre-B cells demonstrated that pre-BCR signaling reduces interactions of both enhancers with Igkappa locus flanking sequences and increases interactions of the 3'kappa enhancer with V(kappa) genes. Remarkably, pre-BCR signaling does not significantly affect interactions between the intronic enhancer and V(kappa) genes, which are already robust in pro-B cells. Both enhancers interact most frequently with highly used V(kappa) genes, which are often marked by transcription factor E2a. We conclude that the kappa enhancers interact with the V(kappa) region already in pro-B cells and that pre-BCR signaling induces accessibility through a functional redistribution of long-range chromatin interactions within the V(kappa) region, whereby the two enhancers play distinct roles. |
