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.

A study from 1998 identified around 40 IEGs,[1] though more recent studies sometimes find more, or cell-type specific IEGs. 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 ZNF268 and Arc have been implicated in learning and memory and long-term potentiation.[2][3]

Memory consolidation during a learning experience depends on the rapid expression of a set of IEGs in brain neurons.[4] 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.[4]

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  1. ^ Worley P, Lanahan A (1998). "Immediate-early genes and synaptic function". Neurobiology of Learning and Memory. 70 (1–2): 37–43. doi:10.1006/nlme.1998.3836. PMID 9753585.
  2. ^ 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. S2CID 41734654.
  3. ^ 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 SG, Bliss TV, Wolfer DP, Kuhl D (2006). "Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories". Neuron. 52 (3): 437–444. doi:10.1016/j.neuron.2006.08.024. PMID 17088210. S2CID 2039086.
  4. ^ a b Li X, Marshall PR, Leighton LJ, Zajaczkowski EL, Wang Z, Madugalle SU, Yin J, Bredy TW, Wei W (Feb 2019). "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. 39 (6): 970–983. doi:10.1523/JNEUROSCI.2024-18.2018. PMC 6363930. PMID 30545945.; Li X, Marshall PR, Leighton LJ, Zajaczkowski EL, Wang Z, Madugalle SU, Yin J, Bredy TW, Wei W (2019). "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. 39 (6): 970–983. doi:10.1523/JNEUROSCI.2024-18.2018. PMC 6363930. PMID 30545945.