MiR290-5p/292-5p activate the immunoglobulin kappa locus in B cell development.

ABSTRACT: 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 Ig? light chain gene (243469) by contributing to the activation of germline Ig? transcription (?GT). 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 ?GT, E2A (21423) and NF-?B (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 ?GT. Furthermore, miR290-5p/292-5p knockdown also diminishes ?GT 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 ?GT induction in miR290 cluster knockout mice. We hypothesize that increased expression of miR290-5p and miR292-5p contributes to the induction of ?GT at the pre-B stage of B cell development through increased binding of NF-?B and E2A to kappa locus regulatory sequences.

SUBMITTER: Garcia PB 

PROVIDER: S-EPMC3426528 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature