The bcl11a transcription factor directly activates RAG gene expression and V(D)J recombination

Academic Article

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. © 2013, American Society for Microbiology.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Lee BS; Dekker JD; Lee BK; Iyer VR; Sleckman BP; Shaffer AL; Ippolito GC; Tuckera PW
  • Start Page

  • 1768
  • End Page

  • 1781
  • Volume

  • 33
  • Issue

  • 9