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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Retracted Publication
MeSH terms
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Amino Acid Sequence
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Animals
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Carrier Proteins / analysis
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cells, Cultured
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DNA-Binding Proteins / genetics*
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Gene Deletion
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Homeodomain Proteins / genetics*
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Humans
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Mice
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Mice, Inbred C57BL
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Nuclear Proteins / analysis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Precursor Cells, B-Lymphoid / metabolism
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Promoter Regions, Genetic
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Protein Isoforms / analysis
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Repressor Proteins
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Transcriptional Activation*
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Up-Regulation
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V(D)J Recombination*
Substances
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BCL11A protein, human
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Bcl11a protein, mouse
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Carrier Proteins
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DNA-Binding Proteins
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Homeodomain Proteins
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Nuclear Proteins
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Protein Isoforms
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Repressor Proteins
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V(D)J recombination activating protein 2
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RAG-1 protein