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IgM receptor-mediated transactivation of the IgH 3' enhancer couples a novel Elf-1-AP-1 protein complex to the developmental control of enhancer function.
- Source :
-
The EMBO journal [EMBO J] 1995 Sep 15; Vol. 14 (18), pp. 4501-13. - Publication Year :
- 1995
-
Abstract
- The function of the temporally regulated B lymphocyte-specific immunoglobulin heavy chain (IgH) 3' enhancer has been linked to the IgH class switch machinery, but the physiological mechanism(s) of activation has not been discerned. Following crosslinking of the IgM receptor, we demonstrate that the enhancer is transactivated in the B lymphoma cell line BAL-17. In both induced primary B lymphocytes and BAL-17 cells, the enhancer activation is concomitant with the recruitment of a novel DNA binding complex, nuclear factor of activated B cells (NFAB). NFAB contains the tissue-restricted Ets protein Elf-1 and the AP-1 factors Jun-B and c-Fos, which bind to a novel 3' enhancer ETS-AP-1 motif. IgM receptor-mediated activation or stimulation by phorbol-ester in BAL-17 cells demonstrates that the ETS-AP-1 motif, when linked to a heterologous gene, can confer a ligand/receptor-dependent response. In NIH 3T3 cells, Elf-1 expression is required for efficient ETS-AP-1 promoter activity in response to stimulation by 12-O-tetradecanylphorbol 13-acetate. Our results suggest a biological role for Elf-1 in the regulation of IgH gene expression, attribute a functional role for receptor-induced AP-1 proteins in B lymphocytes and provide evidence for a direct link between IgM receptor-mediated signalling and 3' enhancer activation.
- Subjects :
- Animals
Base Sequence
Cells, Cultured
Cross-Linking Reagents
DNA Footprinting
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Genes, Reporter
Genetic Complementation Test
Lymphoma, B-Cell
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
Nuclear Proteins metabolism
Protein Binding
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-ets
Structure-Activity Relationship
Transcription Factor AP-1 genetics
Transcription Factor AP-1 metabolism
Transcription Factors genetics
Transcription Factors metabolism
Transfection
Tumor Cells, Cultured
B-Lymphocytes immunology
Enhancer Elements, Genetic
Immunoglobulin Heavy Chains genetics
Receptors, Fc metabolism
Signal Transduction
Transcriptional Activation
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 14
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 7556093
- Full Text :
- https://doi.org/10.1002/j.1460-2075.1995.tb00129.x