Regulation of c-fos gene expression in hamster fibroblasts: initiation and elongation of transcription and mRNA degradation

Abstract

Rapid and transient activation of both c-fos transcription and mRNA accumulation occurs when resting CCL39 hamster fibroblasts are serum-stimulated to grow. By using several combinations of serum and cycloheximide, a protein synthesis inhibitor, we showed that: i) addition of cycloheximide to resting cell elicits an increase in c-fos gene transcription located within the first 540 bases of the unit, suggesting that an "attenuation-like" mechanism, similar to that observed for c-myc, might be essential for c-fos transcriptional regulation; ii) it also prevents both transcriptional shutoff and mRNA degradation in serum-stimulated cells; iii) upon removal of cycloheximide, mRNA degradation resumes rapidly; deletion of a 130 bases long segment in the 3 non-coding region leads to a stabilization of c-fos mRNA lending experimental support to a putative destabilizer element within this sequence.