title: The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination.
abstract: 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.
authors: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA.
authors: Baeck-seung
authors: BS
authors: Lee
authors: Joseph D
authors: JD
authors: Dekker
authors: Bum-kyu
authors: BK
authors: Lee
authors: Vishwanath R
authors: VR
authors: Iyer
authors: Barry P
authors: BP
authors: Sleckman
authors: Arthur L
authors: AL
authors: Shaffer
authors: Gregory C
authors: GC
authors: Ippolito
authors: Philip W
authors: PW
authors: Tucker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D015533:Transcriptional Activation; D015854:Up-Regulation; D060152:V(D)J Recombination
chemical_list: C486563:BCL11A protein, human; C407733:Bcl11a protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein