Immediate early gene

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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. Thus 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.

About 40 cellular IEGs have been identified so far. The earliest known and best characterized 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.

In their role as "gateways to genomic response", many IEG products are naturally transcription factors or other DNA-binding proteins. However, other important classes of IEG products include secreted proteins, cytoskeletal proteins, and receptor subunits.

Some IEGs such as zif268 and Arc have been implicated in learning and memory and long-term potentiation.[1][2]

Memory consolidation during a learning experience depends on the rapid expression of a set of IEGs in brain neurons.[3] 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.[3]

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  1. ^ Davis S, Bozon B, Laroche S (2003). "How necessary is the activation of the immediate early gene zif268 in synaptic plasticity and learning?". Behav Brain Res. 142 (1–2): 17–30. doi:10.1016/S0166-4328(02)00421-7. PMID 12798262.
  2. ^ Plath N, Ohana O, Dammermann B, Errington ML, Schmitz D, Gross C, Mao X, Engelsberg A, Mahike C, Welzi H, Kobalz U, Stawrakakis A, Fernandez E, Walteriet R, Bick-Sander A, Therstappen E, Cooke SF, Blanquet V, Wurst W, Salmen B, Bosl MR, Lipp HP, Grant SGN, Bliss TVP, Wolfer DP, Kuhl D (2006). “Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories.” Neuron. 52:437-444.
  3. ^ a b Li X, Marshall PR, Leighton LJ, Zajaczkowski EL, Wang Z, Madugalle SU, Yin J, Bredy TW, Wei W. The DNA Repair-Associated Protein Gadd45γ Regulates the Temporal Coding of Immediate Early Gene Expression within the Prelimbic Prefrontal Cortex and Is Required for the Consolidation of Associative Fear Memory. J Neurosci. 2019 Feb 6;39(6):970-983. doi: 10.1523/JNEUROSCI.2024-18.2018. Epub 2018 Dec 13. Erratum in: J Neurosci. 2019 May 15;39(20):3993. PMID:30545945