stimulus. It has been shown that there are differences between the response 
of the SRE to TPA in 3T3 cells and Hela cells (Siegfried and Ziff 1989). 
In addition to these upstream transcription factors, there is evidence from at 
least two of the lEGs that there is regulation of transcriptional termination. A 
transcription termination site has been found at the end of the first exon of both 
c -fos and c-myc (Bentley and Groudine 1986; Lamb et al. 1990; Nepveu et al. 
1987; Nepveu and Marcu 1986). The mechanisms by which transcriptional 
termination is regulated in mammalian cells is not clear, but recent studies of 
the human immunodeficiency virus Tat protein indicate that there are promoter- 
specific mechanisms for regulating transcriptional termination of mammalian 
genes (Marciniak et al. 1990). However, it is not known how these termination 
sites are regulated by external cellular signals. 
SUMMARY 
From this brief overview of the regulation of the c -fos promoter, it can be seen 
that the regulation of early-response genes is a complex affair. Therefore, it is 
not easy to predict from the upstream sequence of a given early-response gene 
exactly which elements are responsible for responding to what signals in a 
given cell type. However, from studies of other early-response genes, it is 
clear that several of the elements found upstream of c -fos appear frequently 
and are important in the regulation of other early-response genes. For instance, 
the zifl 268 gene has four separate CArG boxes that are similar to fos. These 
CArG boxes can function in the serum and TPA response, but interestingly, 
they are not imbedded in a region of dyad symmetry as in c -fos (Christy and 
Nathans 1 989). Upstream of the c -jun oncogene is an AP-1 site that can 
modulate the expression and induction of this gene and is responsive to TPA 
(Angel et al. 1988). Moreover, other studies suggest that cAMP-mediated 
signals can repress induction of c -jun through this element (de Groot et al. 
1991; Mechta et al. 1989). This would explain why in certain circumstances, 
such as depolarization of PCI 2 cells or in the striatum in response to cocaine, 
there is an uncoupling of the induction of c -jun and jun- B. Depolarization 
induces c -fos and jun - B but not c -jun\ however, growth factors such as NGF 
can induce all three genes in the same cell (Bartel et al. 1989). Upstream of 
the jun - B gene there does not appear to be an SRE, but there is a new element 
that can be responsive to both cAMP and phorbol esters (de Groot et al. 1991). 
Genes such as c-myc, JE, and KC have no consensus SREs upstream, and the 
regulatory elements responsible for the induction of these genes have not been 
clearly identified (Rollins et al. 1988). However, there is some evidence from 
the c-myc gene that the E2F binding sites are important for its regulation by 
serum (Mudryj et al. 1990; Sacca and Cochran 1990). In addition, there are two 
SIF sites upstream of the c-myc proto-oncogene (B.H. Cochran and T.E. Hayes, 
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