Roles of Ets proteins, NF-kappa B and nocodazole in regulating induction of transcription of mouse germline Ig alpha RNA by transforming growth factor-beta 1

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dc.contributor.authorShi, M. J.
dc.contributor.authorPark, S. R.
dc.contributor.authorKim, P. H.
dc.contributor.authorStavnezer, Janet
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.date2022-08-11T08:11:04.000
dc.date.accessioned2022-08-23T17:31:07Z
dc.date.available2022-08-23T17:31:07Z
dc.date.issued2001-06-01
dc.date.submitted2007-09-14
dc.description.abstractAntibody class switch recombination (CSR) occurs after antigen activation of B cells. CSR is directed to specific heavy chain isotypes by cytokines and B cell activators that induce transcription from the unrearranged, or germline (GL), C(H) region genes. Transforming growth factor (TGF)-beta1 is essential for switch recombination to IgA due to its ability to induce transcription from GL Ig alpha genes. It has been shown that the promoters which regulate transcription of mouse and human GL alpha RNAs contain a TGF-beta1-responsive element that binds Smad and core binding factor (CBFalpha)/AML/PEBPalpha/RUNX: They also contain other elements which bind the transcription factors CREB, BSAP and Ets family proteins. In this manuscript we demonstrate that two tandem Ets sites in the mouse GL alpha promoter bind the transcription factors Elf-1 and PU.1, and that the 3' site is essential for expression of a luciferase reporter gene driven by the GL alpha promoter. Binding of Elf-1 to the GL alpha promoter is inducible by lipopolysaccharide in nuclear extracts from splenic B cells. An NF-kappaB site is identified, although it does not contribute to expression of the promoter in reporter gene assays. Since CSR to IgA is greatly reduced in NF-kappaB/p50-deficient mice, these data support the hypothesis that NF-kappaB has roles in switching in addition to regulation of GL transcription. Finally, we demonstrate that nocodazole, which disrupts microtubules that sequester Smad proteins in the cytoplasm, stimulates transcription from the GL alpha promoter.
dc.identifier.citationInt Immunol. 2001 Jun;13(6):733-46.
dc.identifier.contextkey367648
dc.identifier.issn0953-8178 (Print)
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/wfc_pp/187
dc.identifier.pmid11369700
dc.identifier.submissionpathwfc_pp/187
dc.identifier.urihttps://hdl.handle.net/20.500.14038/50661
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11369700&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://intimm.oxfordjournals.org/content/13/6/733.full.pdf+html
dc.source.issue6
dc.source.journaltitleInternational immunology
dc.source.pages733-46
dc.source.volume13
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectB-Lymphocytes
dc.subjectBase Sequence
dc.subjectBinding Sites
dc.subjectCells, Cultured
dc.subjectDNA-Binding Proteins
dc.subjectGene Expression Regulation
dc.subjectGerm-Line Mutation
dc.subjectHela Cells
dc.subjectHumans
dc.subjectImmunoglobulin A
dc.subjectLymphocyte Activation
dc.subjectMice
dc.subjectMolecular Sequence Data
dc.subjectNF-kappa B
dc.subjectNocodazole
dc.subjectNuclear Proteins
dc.subjectPromoter Regions (Genetics)
dc.subjectProto-Oncogene Proteins
dc.subjectProto-Oncogene Proteins c-ets
dc.subjectRNA
dc.subjectSpleen
dc.subjectTranscription Factors
dc.subjectTransforming Growth Factor beta
dc.subjectTumor Cells, Cultured
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectWomen's Studies
dc.titleRoles of Ets proteins, NF-kappa B and nocodazole in regulating induction of transcription of mouse germline Ig alpha RNA by transforming growth factor-beta 1
dc.typeJournal Article
dspace.entity.typePublication
html.description.abstract<p>Antibody class switch recombination (CSR) occurs after antigen activation of B cells. CSR is directed to specific heavy chain isotypes by cytokines and B cell activators that induce transcription from the unrearranged, or germline (GL), C(H) region genes. Transforming growth factor (TGF)-beta1 is essential for switch recombination to IgA due to its ability to induce transcription from GL Ig alpha genes. It has been shown that the promoters which regulate transcription of mouse and human GL alpha RNAs contain a TGF-beta1-responsive element that binds Smad and core binding factor (CBFalpha)/AML/PEBPalpha/RUNX: They also contain other elements which bind the transcription factors CREB, BSAP and Ets family proteins. In this manuscript we demonstrate that two tandem Ets sites in the mouse GL alpha promoter bind the transcription factors Elf-1 and PU.1, and that the 3' site is essential for expression of a luciferase reporter gene driven by the GL alpha promoter. Binding of Elf-1 to the GL alpha promoter is inducible by lipopolysaccharide in nuclear extracts from splenic B cells. An NF-kappaB site is identified, although it does not contribute to expression of the promoter in reporter gene assays. Since CSR to IgA is greatly reduced in NF-kappaB/p50-deficient mice, these data support the hypothesis that NF-kappaB has roles in switching in addition to regulation of GL transcription. Finally, we demonstrate that nocodazole, which disrupts microtubules that sequester Smad proteins in the cytoplasm, stimulates transcription from the GL alpha promoter.</p>
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