Immediate early genes (IEGs) are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized. IEGs are distinct from "late response" genes, which can only be activated later, following the synthesis of early response gene products. Thus IEGs have been called the "gateway to the genomic response". The term can describe viral regulatory proteins that are synthesized following viral infection of a host cell, or cellular proteins that are made immediately following stimulation of a resting cell by extracellular signals. In their role as "gateways to genomic response", many IEG products are natural transcription factors or other DNA-binding proteins. However, other important classes of IEG products include secreted proteins, cytoskeletal proteins, and receptor subunits. Neuronal IEGs are used prevalently as a marker to track brain activities in the context of memory formation and development of psychiatric disorders. IEGs are also of interest as a therapeutic target for treatment of human cytomegalovirus. Types The earliest identified and best characterized IEGs include c-fos, c-myc and c-jun, genes that were found to be homologous to retroviral oncogenes. Thus IEGs are well known as early regulators of cell growth and differentiation signals. However, other findings suggest roles for IEGs in many other cellular processes. Regulation Expression of IEGs occurs in response to internal and external cell signals, occurring rapidly without the need to synthesize new transcription factors. The genetic sequences of IEGs are generally shorter in length (~19kb) and exhibit an enrichment of specific transcription factor binding sites, offering redundancy in transcription initiation. Translation of IEG mRNA into proteins occurs regardless of protein synthesis inhibitors which disrupts the process of protein production. Rapid expression of IEGs is also attributed to the accessibility of its promotor sequence through histone acetylation that is consistent pre- and post-expression. Downregulation of mRNA transcription occurs through redundant targeting of the 3' UTR region by microRNAs, resulting in translational repression and degradation. The expression of IEG protein is often transient due to rapid mRNA downregulation and increased proteolysis of translated products. Function Activation of gene transcription is a complex system of signal cascades and recruitment of necessary components such as RNA polymerase and transcription factors. IEGs are often the first responders to regulatory signals with many reaching