| First Author | Qiu X | Year | 2018 |
| Journal | Mol Cell | Volume | 70 |
| Issue | 1 | Pages | 21-33.e6 |
| PubMed ID | 29576529 | Mgi Jnum | J:262040 |
| Mgi Id | MGI:6157125 | Doi | 10.1016/j.molcel.2018.02.020 |
| Citation | Qiu X, et al. (2018) Sequential Enhancer Sequestration Dysregulates Recombination Center Formation at the IgH Locus. Mol Cell 70(1):21-33.e6 |
| abstractText | Immunoglobulin heavy-chain (IgH) genes are assembled by DNA rearrangements that juxtapose a variable (VH), a diversity (DH), and a joining (JH) gene segment. Here, we report that in the absence of intergenic control region 1 (IGCR1), the intronic enhancer (Emu) associates with the next available CTCF binding site located close to VH81X via putative heterotypic interactions involving YY1 and CTCF. The alternate Emu/VH81X loop leads to formation of a distorted recombination center and altered DH rearrangements and disrupts chromosome conformation that favors distal VH recombination. Cumulatively, these features drive highly skewed, Emu-dependent recombination of VH81X. Sequential deletion of CTCF binding regions on IGCR1-deleted alleles suggests that they influence recombination of single proximal VH gene segments. Our observations demonstrate that Emu interacts differently with IGCR1- or VH-associated CTCF binding sites and thereby identify distinct roles for insulator-like elements in directing enhancer activity. |
