Immediate early gene

Expression of IEG c-Fos in neurons responding to stimulation with potassium treatment

Some IEGs such as ZNF268 and Arc have been implicated in learning and memory and long-term potentiation.[12][13]

A wide range of neuronal stimulation have been shown to induce IEG expression ranging from sensory and behavioral to drug-induced convulsions.[9] As such, IEGs are utilized as a marker to understand neuronal ensembles associated with formations of certain memories such as fear, commonly attributed to the development of psychiatric disorders.[11] For example, neurons expression Arc in the hippocampus show phenotypic and behavioral differences in response to stimuli such as altered dendritic spine morphology or spontaneous firing rate.[9] This association suggests the expression of certain IEGs in response to a stimulus results in expansion of the related neuronal circuit by incorporating the activated neuron assembles. Other IEGs effect different neural properties with knock out of Arc showing adverse affects on the formation of long-term memory.[9] These findings offer insight into the molecular mechanism and functional changes brought about by IEG expression, expanding the theory of memory trace.

Memory consolidation during a learning experience depends on the rapid expression of a set of IEGs in brain neurons.[14] In general, expression of genes often can be epigenetically repressed by the presence of 5-methylcytosine in the DNA promoter regions of the genes. However, in the case of IEGs associated with memory consolidation demethylation of 5-methylcytosine to form the normal base cytosine can induce rapid gene expression. Demethylation appears to occur by a DNA repair process involving the GADD45G protein.[14]

IEGs are used as markers in animal models of depression. Affected mice have altered levels of Arc,affecting synaptic activity, and EGR1, involved in memory trace encoding.[1] Other neuropsychiatric illnesses such as schizophrenia also exhibit altered IEG expression, with recent studies showing a correlation of low expression of EGR3, a transcription factor downstream of NMDARs, in patients exhibiting schizophrenia.[15] As such, IEGs are crucial markers in evaluating neuronal activity in the context of psychiatric illness with its expression pattern shaped by environmental and genetic factors.[15]

Human Cytomegalovirus is a prevalent beta herpesvirus that remains in the latent state, going unnoticed in healthy individuals with serious consequences if the individual is immunocompromised. The virus cycles in and out of the latent state and is characterized by different gene expression regions: immediate-early (IE), early, and late.[16] Conventional anti-viral treatments such as Ganciclovir use nucleoside analogs to target the early events of the viral replication cycles, however, these approaches are prone to developing resistance.[17] Targeting IE1 and IE2 are thought to be crucial in regulating the pathogenesis of HCMV and retaining the virus in the latent state. Viral proteins derived from IE1 and IE2 regulate viral latency by controlling subsequent expression of early and late genes.[2] Silencing of IE gene expression through antisense oligonucleotides, RNA interference, and gene-targeting ribosomes have been investigated for therapeutic applications.[2][17] Alternatively, the rise of CRISPR technology allows for precise DNA editing that can knockout HCMV genes responsible for IE transcription. DNA targeting is more effective in latent infections, in which viral mRNA is absent or at a low concentration.[2] Small molecule chemical inhibitors are also being investigated that target epigenetic factors and signaling proteins involved in IE expression.[2]