The serum response element and an AP-1/ATF sequence immediately downstream co-operate in the regulation of c-fos transcription.
Transcription of the c-fos gene is activated in response to a wide variety of extracellular stimuli and several cis-acting transcriptional control elements have been characterized. One of these elements is called the serum response element (SRE) and here we investigate an interaction between this element and an AP-1/ATF-like sequence immediately downstream from the SRE. In growing cells these sequences activate transcription in an additive fashion whereas in quiescent cells they co-operate to repress transcription. This co-operation is disrupted upon separation of the elements which also alters the response of the elements to serum or 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation of quiescent cells. This separation also results in an increase of transcription in growing cells. A consensus AP-1 DNA-binding site can substitute for the AP-1/ATF-like sequence present in the c-fos promoter to activate transcription in an additive fashion with the SRE in growing cells, and co-operate in repression in quiescent cells. These observations show that any interaction that may be occurring between proteins binding to these elements results in a different pattern of transcriptional control in growing and quiescent cells. Alternatively, different proteins (or modified proteins) may complex with these sequences in the two different states of cell growth.
Morgan
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IM
Cancer Research Campaign Beatson Laboratories, Beatson Institute for Cancer Research, Glasgow, UK.
Birnie
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GD
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D016762:Genes, fos; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D026362:Serum Response Factor; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D026362:Serum Response Factor