| First Author | Garcia PB | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e43805 |
| PubMed ID | 22928038 | Mgi Jnum | J:191683 |
| Mgi Id | MGI:5462310 | Doi | 10.1371/journal.pone.0043805 |
| Citation | Garcia PB, et al. (2012) miR290-5p/292-5p activate the immunoglobulin kappa locus in B cell development. PLoS One 7(8):e43805 |
| abstractText | Regulated expression of miRNAs influences development in a wide variety of contexts. We report here that miR290-5p (100049710) and miR292-5p (100049711) are induced at the pre-B stage of murine B cell development and that they influence assembly of the Igkappa light chain gene (243469) by contributing to the activation of germline Igkappa transcription (kappaGT). We found that upon forced over-expression of miR290-5p/292-5p in Abelson Murine Leukemia Virus (AMuLV) transformed pro-B cells, two known activators of kappaGT, E2A (21423) and NF-kappaB (19697), show increased chromosomal binding to the kappa intronic enhancer. Conversely, knockdown of miR290-5p/292-5p in AMuLV pro-B cells blunts drug-induced activation of kappaGT. Furthermore, miR290-5p/292-5p knockdown also diminishes kappaGT activation, but not Rag1/2 (19373, 19374) expression, in an IL-7 dependent primary pro-B cell culture system. In addition, we identified a deficiency in kappaGT induction in miR290 cluster knockout mice. We hypothesize that increased expression of miR290-5p and miR292-5p contributes to the induction of kappaGT at the pre-B stage of B cell development through increased binding of NF-kappaB and E2A to kappa locus regulatory sequences. |
