Myocyte enhancer factor-related B-MEF2 is developmentally expressed in B cells and regulates the immunoglobulin J chain promoter.
Immunoglobulin J chain gene expression is induced by the delivery of a lymphokine signal to antigen-activated B cells in a primary immune response. A major interleukin 2 (IL-2)-responsive region that contains two adjacent control elements (JA and JB) exists within the J chain promoter. Transcription factor PU.1 positively regulates J chain gene expression by binding to one of the control elements (JB) in the J chain promoter. In the present study we have determined that a myocyte enhancer factor 2 (MEF2)-related nuclear factor, named B-MEF2, positively regulates the J chain gene promoter activity via the second control element (JA). An in vitro translated MEF2 family member, MEF2C, was found to bind the JA site with identical properties as endogenously expressed B-MEF2 in B cell lines. Moreover, in vivo experiments showed that a dominant negative mutant of MEF2C blocked B-MEF2 regulation of the J chain promoter. Consistent with its role as positive regulator of J chain gene expression, B-MEF2 levels were enhanced in highly differentiated B cells. In addition, induction of an IL-2-responsive presecretor cell line BCL1 with IL-2 or IL-5 (which up-regulates J chain gene expression) resulted in an increased expression of B-MEF2. We conclude that a MEF2-related transcriptional factor, B-MEF2, acts as a stage-specific positive regulator of J chain gene expression in the B cell lineage.
Rao
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Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. RaoSU@PEABD.com
Karray
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Gackstetter
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Koshland
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ME
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007378:Interleukins / Q000494:pharmacology; D064326:MEF2 Transcription Factors; D051379:Mice; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D009687:Nuclear Proteins / Q000032:analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D007144:Immunoglobulin J-Chains; D007378:Interleukins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C578041:Mef2c protein, mouse