| First Author | Ribeiro de Almeida C | Year | 2011 |
| Journal | Immunity | Volume | 35 |
| Issue | 4 | Pages | 501-13 |
| PubMed ID | 22035845 | Mgi Jnum | J:177852 |
| Mgi Id | MGI:5296403 | Doi | 10.1016/j.immuni.2011.07.014 |
| Citation | Ribeiro de Almeida C, et al. (2011) The DNA-Binding Protein CTCF Limits Proximal Vkappa Recombination and Restricts kappa Enhancer Interactions to the Immunoglobulin kappa Light Chain Locus. Immunity 35(4):501-13 |
| abstractText | Regulation of immunoglobulin (Ig) V(D)J gene rearrangement is dependent on higher-order chromatin organization. Here, we studied the in vivo function of the DNA-binding zinc-finger protein CTCF, which regulates interactions between enhancers and promoters. By conditional deletion of the Ctcf gene in the B cell lineage, we demonstrate that loss of CTCF allowed Ig heavy chain recombination, but pre-B cell proliferation and differentiation was severely impaired. In the absence of CTCF, the Igkappa light chain locus showed increased proximal and reduced distal Vkappa usage. This was associated with enhanced proximal Vkappa and reduced Jkappa germline transcription. Chromosome conformation capture experiments demonstrated that CTCF limits interactions of the Igkappa enhancers with the proximal V(kappa) gene region and prevents inappropriate interactions between these strong enhancers and elements outside the Igkappa locus. Thus, although Ig gene recombination can occur in the absence of CTCF, it is a critical factor determining Vkappa segment choice for recombination. |
