SOX10-dependent POU3F1 gene expression

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R-HSA-9613644
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Homo sapiens
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POU3F1, also known as OCT6, is a transcription factor involved in early embyrogenesis and neuronal developement, particularly the myelination of Schwann cells in the peripheral nervous system (Monuki et al, 1990; Jaegle et al, 1996; Ryu et al, 2007; reviewed in Zhao, 2013; Svaren and Meijer, 2008). Expression of POU3F1 in Schwann cells is transient, and peaks at the promyelination stage, and loss of POUF3F1 causese a delay in myelination (Jaegle et al, 2003; Jaegle et al, 1996).
Expression of POU3F1 is driven in part by the Schwann Cell Enhancer (SCE), which is bound by a dimer of SOX10, a key regulator of Schwann cell development (Jagalur et al, 2011). POU3F1 expression is also regulated by the adhesion GPCR ADGRG6 (also known as GPR126). Expression of POU3F1 and EGR2 is lost in grp126 mutant, which arrest at a promyelinating stage (Monk et al, 2009; Monk et al, 2011). ADGRG6 elevates cAMP levels through G alpha s G proteins, and may control POU3F1 expression through the cAMP-PKA-CREB pathway (Morgan et al, 1991; Lee et al, 1999; Mandemakers et al, 2000; Monk et al, 2009; Monk et al, 2011; Mogha et al, 2013; reviewed in Svaren and Meijer). CREB phosphorylation may also be regulated by the NRG1-ERBB2:ERBB3 pathway (reviewedi n Newbern and Birchmeier,2010).
After induction, POU3F1, POU3F2 (also known as OCT7) and SOX10 work together in a feedforward mechanism to activate expression of EGR2, which ultimately promotes expression of genes encoding myelin components, such as myelin protein zero (MPZ) and myelin basic protein (MBP) (Ghislain and Charnay, 2006; Le Blanc et al, 2006; Le Blanc et al, 2007; Marathe et al, 2013; reviewed in Stolt and Wegner, 2016; Svaren and Meijer, 2008)

Literature References
PubMed ID Title Journal Year
21653862 Functional dissection of the Oct6 Schwann cell enhancer reveals an essential role for dimeric Sox10 binding

Jagalur, NB, Ghazvini, M, Mandemakers, W, Driegen, S, Maas, A, Jones, EA, Jaegle, M, Grosveld, F, Svaren, J, Meijer, D

J. Neurosci. 2011
1975954 Expression and activity of the POU transcription factor SCIP

Monuki, ES, Kühn, R, Weinmaster, G, Trapp, BD, Lemke, G

Science 1990
18803322 The molecular machinery of myelin gene transcription in Schwann cells

Svaren, J, Meijer, D

Glia 2008
24227709 Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation

Mogha, A, Benesh, AE, Patra, C, Engel, FB, Schöneberg, T, Liebscher, I, Monk, KR

J. Neurosci. 2013
8662541 The POU factor Oct-6 and Schwann cell differentiation

Jaegle, M, Mandemakers, W, Broos, L, Zwart, R, Karis, A, Visser, P, Grosveld, F, Meijer, D

Science 1996
17959798 Misexpression of Pou3f1 results in peripheral nerve hypomyelination and axonal loss

Ryu, EJ, Wang, JY, Le, N, Baloh, RH, Gustin, JA, Schmidt, RE, Milbrandt, J

J. Neurosci. 2007
23747866 Octamer-binding transcription factors: genomics and functions

Zhao, FQ

Front Biosci (Landmark Ed) 2013
17325040 Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10

Leblanc, SE, Ward, RM, Svaren, J

Mol. Cell. Biol. 2007
23874858 SWI/SNF enzymes promote SOX10- mediated activation of myelin gene expression

Marathe, HG, Mehta, G, Zhang, X, Datar, I, Mehrotra, A, Yeung, KC, de la Serna, IL

PLoS ONE 2013
1704008 The effects of cAMP on differentiation of cultured Schwann cells: progression from an early phenotype (04+) to a myelin phenotype (P0+, GFAP-, N-CAM-, NGF-receptor-) depends on growth inhibition

Morgan, L, Jessen, KR, Mirsky, R

J. Cell Biol. 1991
12782656 The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development

Jaegle, M, Ghazvini, M, Mandemakers, W, Piirsoo, M, Driegen, S, Levavasseur, F, Raghoenath, S, Grosveld, F, Meijer, D

Genes Dev. 2003
19745155 A G protein-coupled receptor is essential for Schwann cells to initiate myelination

Monk, KR, Naylor, SG, Glenn, TD, Mercurio, S, Perlin, JR, Dominguez, C, Moens, CB, Talbot, WS

Science 2009
10220111 Phosphorylation of CREB in axon-induced Schwann cell proliferation

Lee, MM, Badache, A, DeVries, GH

J. Neurosci. Res. 1999
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
10856243 A distal Schwann cell-specific enhancer mediates axonal regulation of the Oct-6 transcription factor during peripheral nerve development and regeneration

Mandemakers, W, Zwart, R, Jaegle, M, Walbeehm, E, Visser, P, Grosveld, F, Meijer, D

EMBO J. 2000
26423937 Schwann cells and their transcriptional network: Evolution of key regulators of peripheral myelination

Stolt, CC, Wegner, M

Brain Res. 2016
20832498 Nrg1/ErbB signaling networks in Schwann cell development and myelination

Newbern, J, Birchmeier, C

Semin. Cell Dev. Biol. 2010
21613327 Gpr126 is essential for peripheral nerve development and myelination in mammals

Monk, KR, Oshima, K, Jörs, S, Heller, S, Talbot, WS

Development 2011
16373334 Direct regulation of myelin protein zero expression by the Egr2 transactivator

Leblanc, SE, Jang, SW, Ward, RM, Wrabetz, L, Svaren, J

J. Biol. Chem. 2006
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