EGR2 gene expression

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R-HSA-9613760
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Homo sapiens
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EGR2 (also known as KROX20) is a member of the Early Growth Response (EGR) gene family encoding sequence-specific Cys2-His2 DNA binding transcription factors. The EGR family are immediate early genes (IEGs) whose expression is rapidly upregulated in response to a number of external stimuli to control activation of genes involved in stress response and differentiation (reviewed in Pagel and Deindl, 2001; Bahrami and Drabløs, 2016). Roles for EGR proteins are well established in the nervous system, with EGR target genes contributing to synaptic plasticity, long-term potentiation, peripheral nerve myelination and NGF-induced neurite outgrowth (reviewed in Perez-Cadahia et al, 2011; Herdegen and Leah, 1998; O'Donovan et al, 1999)
In addition to its other roles, EGR2 is a critical regulator of myelination by Schwann cells in the peripheral nervous system (reviewed in Svaren and Meijer, 2008). Consistent with this, Schwann cells are blocked at the promyelinating stage in EGR2 knockouts in mice (Topilko et al, 1994). Expression of EGR2 during the myelination process is controlled by a myelinating Schwann cell enhancer (MSE) 35 kb downstream of the gene (Ghislain et al, 2002). The MSE is bound by SOX10, POU3F1 and POU3F2 (Ghislain and Charnay, 2006; Reiprich et al, 2010). SOX10 in turn recruits SMARCA4, HDAC1 and HDAC2 to play overlapping but non-redundant roles in activating EGR2 expression (Jacob et al, 2011; Chen et al, 2011; Weider et al, 2012).

Literature References
PubMed ID Title Journal Year
21423191 HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination

Chen, Y, Wang, H, Yoon, SO, Xu, X, Hottiger, MO, Svaren, J, Nave, KA, Kim, HA, Olson, EN, Lu, QR

Nat. Neurosci. 2011
21423190 HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells

Jacob, C, Christen, CN, Pereira, JA, Somandin, C, Baggiolini, A, Lötscher, P, Ozçelik, M, Tricaud, N, Meijer, D, Yamaguchi, T, Matthias, P, Suter, U

Nat. Neurosci. 2011
18803322 The molecular machinery of myelin gene transcription in Schwann cells

Svaren, J, Meijer, D

Glia 2008
22053691 Early growth response 1--a transcription factor in the crossfire of signal transduction cascades

Pagel, JI, Deindl, E

Indian J. Biochem. Biophys. 2011
10203854 The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience

O'Donovan, KJ, Tourtellotte, WG, Millbrandt, J, Baraban, JM

Trends Neurosci. 1999
22814607 Chromatin-remodeling factor Brg1 is required for Schwann cell differentiation and myelination

Weider, M, Küspert, M, Bischof, M, Vogl, MR, Hornig, J, Loy, K, Kosian, T, Müller, J, Hillgärtner, S, Tamm, ER, Metzger, D, Wegner, M

Dev. Cell 2012
9858769 Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins

Herdegen, T, Leah, JD

Brain Res. Brain Res. Rev. 1998
7935840 Krox-20 controls myelination in the peripheral nervous system

Topilko, P, Schneider-Maunoury, S, Levi, G, Baron-Van Evercooren, A, Chennoufi, AB, Seitanidou, T, Babinet, C, Charnay, P

Nature 1994
11782409 Characterisation of cis-acting sequences reveals a biphasic, axon-dependent regulation of Krox20 during Schwann cell development

Ghislain, J, Desmarquet-Trin-Dinh, C, Jaegle, M, Meijer, D, Charnay, P, Frain, M

Development 2002
19922439 Activation of Krox20 gene expression by Sox10 in myelinating Schwann cells

Reiprich, S, Kriesch, J, Schreiner, S, Wegner, M

J. Neurochem. 2010
16311519 Control of myelination in Schwann cells: a Krox20 cis-regulatory element integrates Oct6, Brn2 and Sox10 activities

Ghislain, J, Charnay, P

EMBO Rep. 2006
21326363 Activation and function of immediate-early genes in the nervous system

Pérez-Cadahía, B, Drobic, B, Davie, JR

Biochem. Cell Biol. 2011
27220739 Gene regulation in the immediate-early response process

Bahrami, S, Drabløs, F

Adv Biol Regul 2016
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