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

Baeck Seung Lee, Joseph D. Dekker, Bum Kyu Lee, Vishwanath R. Iyer, Barry P. Sleckman, Arthur L. Shaffer, Gregory C. Ippolito, Philip W. Tuckera

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1768-1781
Number of pages14
JournalMolecular and Cellular Biology
Volume33
Issue number9
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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