Repression of c-fos transcription is mediated through p67SRF bound to the SRE

Human c-fos expression is subject to tight transcriptional control. The gene is expressed at a high, constitutive level in some cell types and at a very low, but rapidly inducible level in many others. Induction of transcription by serum growth factors is mediated by the serum response element (SRE) to which at least two transcription factors, p67SRF and p62, bind. In this paper it is demonstrated that the low basal level of transcription is mediated through p67SRF bound to the SRE and that high, constitutive expression is observed when binding is prohibited. In this situation, an AP-1 consensus binding site adjacent to the SRE permits transactivation of the gene. Thus three levels of c-fos expression, induced, repressed and constitutive, appear to be determined by occupation of the SRE by p67SRF and its interaction with other proteins.