Mutation of the c-fos gene dyad symmetry element inhibits serum inducibility of transcription in vivo and the nuclear regulatory factor binding in vitro.

Abstract

In vitro mutagenesis of a 61-base-pair DNA sequence element that is necessary for induction of the c-fos proto-oncogene by growth factors revealed that a small region of dyad symmetry within the sequence element is critical for c-fos transcriptional activation. The same c-fos dyad symmetry element was found to bind a nuclear protein in vitro, causing a specific mobility shift of this c-fos regulatory sequence. An analysis of insertion and deletion mutants established a strict correlation between the ability of the dyad symmetry element to promote serum activation of c-fos transcription and in vitro nuclear protein binding. These experiments suggest that the DNA mobility shift assay detects a nuclear protein that mediates growth factor stimulation of c-fos expression. In vitro competition experiments indicate that the c-fos regulatory factor also binds to sequences within another growth factor-inducible gene, the I-actin gene.

Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene

“…Instead, the dissimilarities proved more apparent. TPA and serum act through well-described transcriptional mechanisms to drive c-fos and c-myc expression [25,26,27,44,45]; we found little evidence that similar mechanisms regulate ODC. We have shown instead that TPA and serum can exert a strong regulatory influence on the expression of ODC through posttranscriptional mechanisms and that mitogenic induction of ODC activity depends at least in part on lability of the enzyme.…”

Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes.

“…The SRE is required for the induction of c-fos expression by factors in serum (16,18,34,48). Here it is shown that the chicken skeletal actin promoter is similar to the c-fos promoter in that it can also be induced by serum (Fig.…”

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

“…The induction of c-fos transcription is mediated by several promoter elements . Among these, the Serum Response Element (SRE) is believed to play a central regulatory (Treisman, 1994(Treisman, , 1995, as this sequence has been shown to be necessary and su cient for the rapid induction of c-fos by most growth-promoting stimuli (Greenberg et al, 1987;Johansen and Prywes, 1994). A number of proteins that bind the c-fos SRE can mediate SRE-dependent transcription (Treisman, 1994(Treisman, , 1995, including a transcription factor of 67 kD, termed Serum Response Factor (SRF), that binds the SRE in vivo and in vitro as a dimer (Treisman, 1994(Treisman, , 1995.…”