unpublished results). Upstream of the nur - 77 gene there are no SREs, but 
there are four potential calcium/CRE-like elements (Watson and Milbrandt 
1989). Thus, although most of these early-response genes can be isolated 
from a differential screening of cDNA library in response to a single inducer 
such as PDGF, the regulation of each is unique. In addition, there is much 
more to understand about how some of the early-response genes such as that 
of IL-2 or the IL-2 receptor are expressed as both tissue-specific and lEGs. It is 
likely that the tissue-specific expression of early-response genes is due to a 
combination of chromatin accessibility of the gene and interaction with universal 
regulatory elements as well as tissue-specific regulatory factors (Greene et al. 
1989; Phan-Dinh-Tuy et al. 1988). 
The finding that many early-response genes are induced in the nervous system 
in response to neurotransmitters and other physiological stimuli may indicate 
that these genes have an important role to play in the function of the nervous 
system. (For review, see Sheng and Greenberg [1990] and other chapters in 
this monograph.) The functions of the early-response genes are undoubtedly 
as varied as the gene products. However, many of these genes do appear to 
be transcriptional regulatory factors and therefore are likely to modulate the 
expression of other genes. Work on identifying the targets of these transcription 
factors is still in the early stages. Interestingly, there is already evidence that 
two important neurotransmitter genes, the proenkephalin and the prodynorphin 
genes, may be regulated by an AP-1 complex (Naranjo et al. 1991; Sonnenberg 
et al. 1989b). Thus, one of the roles of early-response genes in the nervous 
system may be to regulate the levels of neurotransmitters in a particular neuron. 
One role that has been suggested for these genes is that they mediate between 
short-term signaling and long-term changes in the nervous system (Morgan 
and Curran 1989). This is especially intriguing, since many studies have 
implicated cAMP in the formation of long-term memory through transcriptional 
changes in the nervous system (Goelet et al. 1986). However, as the induction 
of lEGs is transient, it is not yet clear how these genes would mediate such 
long-term changes. They could be regulating the expression of structural 
genes that could contribute to the formation of synapses and other structural 
changes within neurons. Alternatively, early-response genes could serve as 
a reset mechanism that functions to replenish and restore supplies of 
neurotransmitters that have been utilized. Another possible role for early- 
response genes would be to modulate in the intermediate term the temporal 
patterns of spike trains of given neurons. Since these genes are expressed 
on a time scale of hours, they could contribute to short-term adaptive changes 
in the activity of a given neuron. Obtaining the answers to questions like these 
should be the focus of future research. 
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