Antisense mapping of the c-fos promoter: role of the serum response element.

Using an antisense RNA approach to eliminate endogenous expression of the c-fos protein, we have verified by nuclear run-on and transient expression assays that the Fos protein is a negative regulator of its own transcription in vivo. The negative autoregulation of the c-fos promoter by Fos was further confirmed by overexpression of an antisense-resistant c-fos expressing vector. Antisense mapping of the c-fos promoter demonstrated that the serum responsive element (SRE) represents the major site for c-fos suppression only during the first hour, but that additional adjacent DNA sequences are required for suppression at later times. We propose that antisense inhibition of transcriptional repressors provides a useful method for analyzing the significance and mechanism of transcriptional repression in vivo.