Abstract
Activated mature B cells in which the DNA-binding activity of E-proteins has been disrupted fail to undergo class switch recombination. Here we show that activated B cells overexpressing the antagonist helix-loop-helix protein Id3 do not induce expression of the murine Aicda gene encoding activation-induced deaminase (AID). A highly conserved intronic regulatory element in Aicda binds E-proteins both in vitro and in vivo. The transcriptional activity of this element is regulated by E-proteins. We show that the enforced expression of AID in cells overexpressing Id3 partially restores class switch recombination. Taken together, our observations link helix-loop-helix activity and Aicda gene expression in a common pathway, in which E-protein activity is required for the efficient induction of Aicda transcription.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Base Sequence
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Cytidine Deaminase / biosynthesis*
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Cytidine Deaminase / genetics
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Cytidine Deaminase / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Enhancer Elements, Genetic / immunology
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Enzyme Activation
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Female
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Gene Expression Regulation, Enzymologic / immunology*
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Helix-Loop-Helix Motifs / immunology
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Immunoglobulin Class Switching / immunology
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Immunoglobulin Isotypes / immunology
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Signal Transduction / immunology
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / genetics
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Transcription Factors / immunology*
Substances
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DNA-Binding Proteins
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Immunoglobulin Isotypes
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TCF Transcription Factors
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Tcf7l1 protein, mouse
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Transcription Factor 7-Like 1 Protein
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Transcription Factors
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase