Functional analysis of the OCA-B promoter.
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.
Stevens
S
S
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
Wang
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L
Roeder
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RG
D051701:Activating Transcription Factor 4; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D003994:Bucladesine / Q000494:pharmacology; D019013:CD40 Antigens / Q000276:immunology; D002460:Cell Line; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D016297:Mutagenesis, Site-Directed; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000276:immunology*; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
C081452:Atf4 protein, mouse; D019013:CD40 Antigens; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D007106:Immune Sera; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; C091546:POU2AF1 protein, human; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051701:Activating Transcription Factor 4; D015847:Interleukin-4; D003994:Bucladesine