SOX10 and PAX3 bind the MITF promoter

Stable Identifier
R-HSA-9730407
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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SOX10 and PAX3 bind the MITF promoter
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SOX10 and PAX3 bind directly to cognate elements in the proximal MITF-M promoter to synergistically stimulate its transcription (Zhang et al, 2012; Potterf et al, 2000; Bondurand et al, 2000; Watanabe et al, 1998; reviewed in Mort, 2015; White and Ton, 2008; Goding and Arnheiter, 2019).
PAX3 is a DNA-binding transcription factor with roles in neural development and myogenesis that is expressed in the neural tube prior to neural crest migration (reviewed in Monsoro-Burq, 2015). PAX3 contains a homeobox domain and a paired domain that bind to consensus sequences ATTAAT and GGAAC, respectively (Chalepakis et al, 1994a,b). Consensus binding sites for PAX3 containing these elements have been identified in the promoter of the MITF gene (Watanabe et al, 1998; reviewed in Goding and Arnheiter, 2019).
SOX10 is a member of the sex-determining factor (SRY)-like, high mobility group family of transcription factors that are involved in cell lineage pathways (Schock and LaBonne, 2020). SOX10 is expressed in early migrating neural crest cells, some of which go on to develop into melanoblasts and melanocytes (Herbarth et al 1998; Pusch et al 1998; reviewed in Mort et al, 2015; White and Zon, 2008). SOX10 binding sites have been identified in the proximal and distal regions of the MITF promoter. These sites stimulate expression of reporter genes in vitro, are bound by SOX10 as assessed by electrophoretic mobility shift assays, and drive in vivo expression in mice (Bondurand et al, 2000; Potterf et al, 2000; Zhang et al, 2012; reviewed in Goding and Arnheiter, 2019).
SOX10 transcription factor activity is regulated by SUMOylation, and SOX10 has been shown to be sumoylated at lysine 55 in a UBE2I (also known as UBC9)-dependent manner (Girard et al, 2006; Taylor and La Bonne, 2005; Han et al, 2018). MAPK1-dependent phosphorylation of SOX10 at residues T240 and T244 interferes with the interaction of SOX10 with UBE2I and inhibits SOX10 transcription factor activity at the MITF promoter (Han et al, 2018). A direct transcriptional activation role for SOX10 K55 sumoylation at the MITF promoter has not been shown, however.
Literature References
PubMed ID Title Journal Year
16494873 Sumoylation of the SOX10 transcription factor regulates its transcriptional activity

Girard, M, Goossens, M

FEBS Lett 2006
33424631 Sorting Sox: Diverse Roles for Sox Transcription Factors During Neural Crest and Craniofacial Development

Schock, EN, LaBonne, C

Front Physiol 2020
9500554 Epistatic relationship between Waardenburg syndrome genes MITF and PAX3

Watanabe, A, Takeda, K, Ploplis, B, Tachibana, M

Nat Genet 1998
21965087 Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II

Zhang, H, Chen, H, Luo, H, An, J, Sun, L, Mei, L, He, C, Jiang, L, Jiang, W, Xia, K, Li, JD, Feng, Y

Hum Genet 2012
31123060 MITF-the first 25 years

Goding, CR, Arnheiter, H

Genes Dev 2019
18786412 Melanocytes in development, regeneration, and cancer

White, RM, Zon, LI

Cell Stem Cell 2008
26410165 PAX transcription factors in neural crest development

Monsoro-Burq, AH

Semin Cell Dev Biol 2015
7809114 Pax-3 contains domains for transcription activation and transcription inhibition

Chalepakis, G, Jones, FS, Edelman, GM, Gruss, P

Proc Natl Acad Sci U S A 1994
10982026 Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3

Potterf, SB, Furumura, M, Dunn, KJ, Arnheiter, H, Pavan, WJ

Hum Genet 2000
9560246 Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease

Herbarth, B, Pingault, V, Bondurand, N, Kuhlbrodt, K, Hermans-Borgmeyer, I, Puliti, A, Lemort, N, Goossens, M, Wegner, M

Proc Natl Acad Sci U S A 1998
10942418 Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome

Bondurand, N, Pingault, V, Goerich, DE, Lemort, N, Sock, E, Le Caignec, C, Wegner, M, Goossens, M

Hum Mol Genet 2000
8065927 Pax-3-DNA interaction: flexibility in the DNA binding and induction of DNA conformational changes by paired domains

Chalepakis, G, Wijnholds, J, Gruss, P

Nucleic Acids Res 1994
9760192 The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor

Pusch, C, Hustert, E, Pfeifer, D, Sudbeck, P, Kist, R, Roe, B, Wang, Z, Balling, R, Blin, N, Scherer, G

Hum Genet 1998
29295999 ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma

Han, S, Ren, Y, He, W, Liu, H, Zhi, Z, Zhu, X, Yang, T, Rong, Y, Ma, B, Purwin, TJ, Ouyang, Z, Li, C, Wang, X, Wang, X, Yang, H, Zheng, Y, Aplin, AE, Liu, J, Shao, Y

Nat Commun 2018
25670789 The melanocyte lineage in development and disease

Mort, RL, Jackson, IJ, Patton, EE

Development 2015
16256735 SoxE factors function equivalently during neural crest and inner ear development and their activity is regulated by SUMOylation

Taylor, KM, LaBonne, C

Dev Cell 2005
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Authored
Rothfels, K  (2023-01-26)
Reviewed
Arnheiter, H  (2024-02-26)
de la Serna, IL  (2024-05-21)
Vu, HN  (2024-11-05)
Steingrímsson, E  (2024-11-05)
Created
Rothfels, K  (2021-05-07)
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