First Author | Lee BS | Year | 2013 |
Journal | Mol Cell Biol | Volume | 33 |
Issue | 9 | Pages | 1768-81 |
PubMed ID | 23438597 | Mgi Jnum | J:203755 |
Mgi Id | MGI:5528627 | Doi | 10.1128/MCB.00987-12 |
Citation | Lee BS, et al. (2013) The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination. Mol Cell Biol 33(9):1768-81 |
abstractText | Recombination-activating gene 1 protein (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The transcription factor BCL11A is required for B cell development, but its molecular function(s) in B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds the RAG1 promoter and Erag enhancer to activate RAG1 and RAG2 transcription in pre-B cells. We employed BCL11A overexpression with recombination substrates in a cultured pre-B cell line as well as Cre recombinase-mediated Bcl11a(lox/lox) deletion in explanted murine pre-B cells to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination. |