Regulation of Immediate Early Gene 
Expression 
Brent H. Cochran 
INTRODUCTION 
Recently, much excitement has been generated by the finding that various 
immediate early genes (lEGs) are expressed in neurons in response to a 
variety of neurotropic stimuli. Part of the reason these findings have generated 
so much interest is that earlier work has suggested that long-term changes in 
nervous system behavior require changes in gene expression (Goelet et al. 
1986). Thus, since changes in IEG expression are coupled to neuronal activity 
and neurotransmitter release, it may now be possible, using in situ techniques 
that provide resolution at the single-cell level, to correlate the physiological state 
of a neuron with behavioral and physiological outputs. This chapter reviews 
what is currently known about lEGs and speculates on what roles these genes 
might be playing in the operation of the nervous system. 
lEGs (sometimes called early-response genes or primary-response genes) 
were first identified not in the nervous system but through the study of cell 
growth regulation. During the 1970s it became apparent that polypeptide 
growth factors were key modulators of cell growth and differentiation of 
multicellular organisms. Early studies had suggested that the mitogenic effects 
of serum growth factors were mediated in part by the ability of these factors to 
regulate gene expression (Smith and Stiles 1981). To identify such genes, 
several investigators set out to clone them by differential or subtractive cDNA 
cloning. The first of such genes cloned were those induced by the platelet- 
derived growth factor (PDGF) in 3T3 fibroblasts (Cochran et al. 1983). The 
genes cloned in this study displayed regulatory properties that are characteristic 
of most early-response genes now known. These genes are induced rapidly 
within 1 hour of growth factor treatment and are regulated at the level of 
transcription (Cochran et al. 1988). They are induced by polypeptide growth 
factors that bind to cell surface receptors in the absence of new protein 
synthesis. Therefore, the induction of these genes is a primary response to 
events at the cell surface and not secondary to other waves of gene expression 
or changes in growth state of the cell. The ability of early-response genes to be 
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