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dc.contributor.authorDelphin, S.
dc.contributor.authorStavnezer, Janet
dc.date2022-08-11T08:11:04.000
dc.date.accessioned2022-08-23T17:31:13Z
dc.date.available2022-08-23T17:31:13Z
dc.date.issued1995-09-29
dc.date.submitted2007-09-14
dc.identifier.citation<p>Ann N Y Acad Sci. 1995 Sep 29;764:123-35.</p>
dc.identifier.issn0077-8923 (Print)
dc.identifier.doi10.1111/j.1749-6632.1995.tb55815.x
dc.identifier.pmid7486511
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50683
dc.description.abstractA large body of data indicate that antibody class switching is directed by cytokines by inducing or repressing transcription from unrearranged, or germline, CH genes. IL-4 induces transcription of the germline C epsilon genes in activated B cells, and subsequently cells in this population will undergo switch recombination to IgE. Furthermore, the data suggest that transcription of germline C epsilon genes is required for class switching. In this paper we define DNA elements required for induction of transcription of the germline C epsilon genes by IL-4. To do this, segments of DNA from the 5' flank of the initiation sites for germline epsilon RNA were ligated to a luciferase reporter gene and transfected into two mouse B-cell lines, one of which can be induced to switch to IgE. By analysis of a series of 5' deletion constructs and linker-scanning mutations, we demonstrate that a 46-bp segment (residing at -126/-79 relative to the first RNA initiation site) contains an IL-4 responsive region. This segment binds three transcription factors: the recently described NF-IL4, one or more members of the C/EBP family of transcription factors, and NF-kappa B/p50. Mutation of any of the binding sites for these three factors abolishes or reduces IL-4 inducibility of the epsilon promoter. A 27-bp segment within this IL-4 response region containing binding sites for NF-IL4 and a C/EBP factor is sufficient to transfer IL-4 inducibility to a minimal c-fos promoter.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7486511&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1111/j.1749-6632.1995.tb55815.x
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectBinding Sites
dc.subjectDNA-Binding Proteins
dc.subjectGene Expression Regulation
dc.subject*Genes, Immunoglobulin
dc.subjectGenes, Reporter
dc.subjectHumans
dc.subject*Immunoglobulin Class Switching
dc.subjectImmunoglobulin Constant Regions
dc.subjectImmunoglobulin E
dc.subjectImmunoglobulin Heavy Chains
dc.subjectInterleukin-4
dc.subjectLuciferases
dc.subjectMice
dc.subjectMolecular Sequence Data
dc.subjectMutagenesis, Site-Directed
dc.subject*Promoter Regions (Genetics)
dc.subjectSequence Alignment
dc.subjectSequence Homology, Nucleic Acid
dc.subjectTranscription Factors
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectWomen's Studies
dc.titleRegulation of antibody class switching to IgE: characterization of an IL-4-responsive region in the immunoglobulin heavy-chain germline epsilon promoter
dc.typeJournal Article
dc.source.journaltitleAnnals of the New York Academy of Sciences
dc.source.volume764
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/wfc_pp/208
dc.identifier.contextkey367669
html.description.abstract<p>A large body of data indicate that antibody class switching is directed by cytokines by inducing or repressing transcription from unrearranged, or germline, CH genes. IL-4 induces transcription of the germline C epsilon genes in activated B cells, and subsequently cells in this population will undergo switch recombination to IgE. Furthermore, the data suggest that transcription of germline C epsilon genes is required for class switching. In this paper we define DNA elements required for induction of transcription of the germline C epsilon genes by IL-4. To do this, segments of DNA from the 5' flank of the initiation sites for germline epsilon RNA were ligated to a luciferase reporter gene and transfected into two mouse B-cell lines, one of which can be induced to switch to IgE. By analysis of a series of 5' deletion constructs and linker-scanning mutations, we demonstrate that a 46-bp segment (residing at -126/-79 relative to the first RNA initiation site) contains an IL-4 responsive region. This segment binds three transcription factors: the recently described NF-IL4, one or more members of the C/EBP family of transcription factors, and NF-kappa B/p50. Mutation of any of the binding sites for these three factors abolishes or reduces IL-4 inducibility of the epsilon promoter. A 27-bp segment within this IL-4 response region containing binding sites for NF-IL4 and a C/EBP factor is sufficient to transfer IL-4 inducibility to a minimal c-fos promoter.</p>
dc.identifier.submissionpathwfc_pp/208
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.source.pages123-35


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