Temporal recruitment of the mSin3A-histone deacetylase corepressor complexto the ETS domain transcription factor Elk-1

The transcriptional status of eukaryotic genes is determined by a balance b etween activation and repression mechanisms. The nuclear hormone receptors represent classical examples of transcription factors that can regulate thi s balance by recruiting corepressor and coactivator complexes in a ligand-d ependent manner. Were, we demonstrate that the equilibrium between activati on and repression via a single transcription factor, Elk-1, is altered foll owing activation of the Erk mitogen-activated protein kinase cascade. In ad dition 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 p romoters, c-fos, Elk-1 therefore undergoes temporal activator-repressor swi tching and contributes to both the activation and repression of target gene s following growth factor stimulation.