| First Author | Kleiman E | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 6 | Pages | 1633-1638 |
| PubMed ID | 30076197 | Mgi Jnum | J:265214 |
| Mgi Id | MGI:6199372 | Doi | 10.4049/jimmunol.1800785 |
| Citation | Kleiman E, et al. (2018) Cutting Edge: Proper Orientation of CTCF Sites in Cer Is Required for Normal Jkappa-Distal and Jkappa-Proximal Vkappa Gene Usage. J Immunol 201(6):1633-1638 |
| abstractText | Igkappa locus contraction and Vkappa gene usage are controlled by Cer, a cis-acting sequence in the Vkappa-Jkappa intervening region. This effect is attributed to two CTCF-binding sites within Cer that are oriented toward the Vkappa gene region. However, the importance of Cer CTCF orientation in regulating VkappaJkappa rearrangement is unknown. We used CRISPR/Cas9 editing to delete and invert Cer in murine Abl pro-B cell lines. This revealed that Cer orientation is critical because clones with either an inverted or deleted Cer element show skewing toward Jkappa-proximal Vkappa gene usage. However, only Cer deletion increased Jkappa-proximal Vkappa germline transcription, suggesting an insulating function of Cer. Lastly, circularized chromosome conformation capture interaction data show that Cer CTCF orientation regulates long-range interactions with inversion clones displaying fewer interactions with regions in the middle and distal parts of the Vkappa locus and more interactions to downstream regions compared with wild-type or deletion clones. |
