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

Baeck-Seung Lee; Bum-Kyu Lee; Vishwanath R Iyer; Barry P Sleckman; Arthur L Shaffer 3rd; Gregory C Ippolito; Haley O Tucker; Joseph D Dekker

doi:10.1128/MCB.00362-17

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

Mol Cell Biol. 2017 Dec 13;38(1):e00362-17. doi: 10.1128/MCB.00362-17. Print 2018 Jan 1.

Authors

Baeck-Seung Lee^{1

2}, Bum-Kyu Lee^{1

2}, Vishwanath R Iyer^{1

2}, Barry P Sleckman³, Arthur L Shaffer 3rd⁴, Gregory C Ippolito^{1

2}, Haley O Tucker^{5

2}, Joseph D Dekker^{5

2}

Affiliations

¹ Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
² Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA.
³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
⁴ Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
⁵ Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA haleytucker@austin.utexas.edu joedekk@utexas.edu.

Abstract

Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining [V(D)J] segment recombination, an essential process for antigen receptor expression and lymphocyte development. The BCL11A transcription factor is required for B cell and plasmacytoid dendritic cell (pDC) development, but its molecular function(s) in early B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds directly to the RAG1 promoter as well as directly to regulatory regions of transcription factors previously implicated in both B cell and pDC development to activate RAG1 and RAG2 gene transcription in pro- and pre-B cells. We employed BCL11A overexpression with recombination substrates 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.

Keywords: B cell development; Bcl11a; RAG; V(D)J; immunology.

Publication types

Published Erratum
Corrected and Republished Article