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.

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Retraction for Lee et al., “The BCL11A Transcription Factor Directly Activates RAG Gene Expression and V(D)J Recombination”

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Corrected and Republished from: BCL11A Is a Critical Component of a Transcriptional Network That Activates RAG Expression and V(D)J Recombination

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Articles of Significant Interest Selected from This Issue by the Editors

ACKNOWLEDGMENTS

We thank Chhaya Das, Maya Ghosh, and June Harriss for excellent technical support. We thank Mark Schlissel for sharing luciferase constructs. We thank members of our laboratory for critically reading the manuscript and Paul Das for its preparation.

G.C.I. acknowledges support from NIH grant F32-CA110624, and P.W.T. acknowledges support from NIH grant RO1-CA31534, the Cancer Prevention Research Institute (grant CPRIT RP100612), and the Marie Betzner Morrow Endowment.