Temporal recruitment of the mSin3A-histone deacetylase corepressor complex to the ETS domain transcription factor Elk-1.
The transcriptional status of eukaryotic genes is determined by a balance between activation and repression mechanisms. The nuclear hormone receptors represent classical examples of transcription factors that can regulate this balance by recruiting corepressor and coactivator complexes in a ligand-dependent manner. Here, we demonstrate that the equilibrium between activation and repression via a single transcription factor, Elk-1, is altered following activation of the Erk mitogen-activated protein kinase cascade. In addition to its C-terminal transcriptional activation domain, Elk-1 contains an N-terminal transcriptional repression domain that can recruit the mSin3A-histone deacetylase 1 corepressor complex. Recruitment of this corepressor is enhanced in response to activation of the Erk pathway in vivo, and this recruitment correlates kinetically with the shutoff of one of its target promoters, c-fos. Elk-1 therefore undergoes temporal activator-repressor switching and contributes to both the activation and repression of target genes following growth factor stimulation.
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
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Yang
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Vickers
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A
Brehm
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Kouzarides
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Sharrocks
D001693:Biological Transport, Active; D002460:Cell Line; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor / Q000494:pharmacology; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D046911:Macromolecular Substances; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010449:Peptide Mapping; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004815:Epidermal Growth Factor; D020928:Mitogen-Activated Protein Kinases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex