Abstract
OCA-B was identified as a B cell-specific coactivator that functions with either Oct-1 or Oct-2 to mediate efficient cell type-specific transcription via the octamer site (ATGCAAAT) both in vivo and in vitro. Mice lacking OCA-B exhibit normal Ag-independent B cell maturation. In contrast, Ag-dependent functions, including production of secondary Ig isotypes and germinal center formation, are greatly affected. To better understand OCA-B expression and, ultimately, the defects observed in the OCA-B knockout mice, we have cloned the OCA-B promoter and examined its function in both transformed and primary B cells. We show here that the OCA-B promoter is developmentally regulated, with activity increasing throughout B cell differentiation. Through physical and functional assays, we have found an activating transcription factor/cAMP response element binding protein binding site (or cAMP response element) that is crucial for OCA-B promoter activity. Furthermore, we demonstrate that IL-4 and anti-CD40 induce both the OCA-B promoter and octamer-dependent promoters, thus implicating OCA-B in B cell signaling events in the nucleus.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activating Transcription Factor 4
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Animals
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Base Sequence
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Binding Sites / drug effects
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Binding Sites / genetics
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Binding Sites / immunology
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Bucladesine / pharmacology
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CD40 Antigens / immunology
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Cell Line
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Cloning, Molecular
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / immunology
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Humans
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Immune Sera / pharmacology
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Interleukin-4 / pharmacology
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Multigene Family / immunology
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Mutagenesis, Site-Directed
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NFATC Transcription Factors
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Nuclear Proteins*
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Promoter Regions, Genetic / drug effects
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Promoter Regions, Genetic / immunology*
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Sequence Analysis, DNA
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Trans-Activators / genetics*
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Trans-Activators / immunology*
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Trans-Activators / metabolism
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Trans-Activators / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Tumor Cells, Cultured
Substances
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Atf4 protein, mouse
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CD40 Antigens
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Immune Sera
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NFATC Transcription Factors
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Nuclear Proteins
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POU2AF1 protein, human
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Pou2af1 protein, mouse
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Trans-Activators
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Transcription Factors
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Activating Transcription Factor 4
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Interleukin-4
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Bucladesine