This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and determination of cell fate. The encoded protein act as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development.[4]
In melanocytic cells there is evidence that SOX10 gene expression may be regulated by MITF.[5]
The interaction between SOX10 and PAX3 is studied best in human patients with Waardenburg syndrome, an autosomal dominant disorder which is divided into four different types based upon mutations in additional genes. SOX10 and PAX3 interactions are thought to be regulators of other genes involved in the symptoms of Waardenburg syndrome, particularly MITF which influences the development of melanocytes as well as neural crest formation. MITF expression can be transactivated by both SOX10 and PAX3 to have an additive effect.[7][8] The two genes have binding sites near one another on the upstream enhancer of the c-RET gene.[9]
SOX10 is also thought to target dopachrome tautomerase through a synergistic interaction with MITF which then results in other melanocyte alteration.[10]
SOX10 can influence the generation of myelin protein transcription through its interactions proteins such as OLIG1 and EGR2,[11][12] which is important for the functionality of neurons. Other cofactors have been identified, such as SP1, OCT6, NMI, FOXD3 and SOX2[13]
The interaction between SOX10 and NMI seems to be coexpressed in glial cells, gliomas, and the spinal cord and has been shown to modulate the transcriptional activity of SOX10.[14]
↑Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Préhu MO, Puliti A, Herbarth B, Hermans-Borgmeyer I, Legius E, Matthijs G, Amiel J, Lyonnet S, Ceccherini I, Romeo G, Smith JC, Read AP, Wegner M, Goossens M (Feb 1998). "SOX10 mutations in patients with Waardenburg-Hirschsprung disease". Nature Genetics. 18 (2): 171–3. doi:10.1038/ng0298-171. PMID9462749.
↑Bondurand N, Kuhlbrodt K, Pingault V, Enderich J, Sajus M, Tommerup N, Warburg M, Hennekam RC, Read AP, Wegner M, Goossens M (Sep 1999). "A molecular analysis of the yemenite deaf-blind hypopigmentation syndrome: SOX10 dysfunction causes different neurocristopathies". Human Molecular Genetics. 8 (9): 1785–9. doi:10.1093/hmg/8.9.1785. PMID10441344.
↑Huber WE, Price ER, Widlund HR, Du J, Davis IJ, Wegner M, Fisher DE (Nov 2003). "A tissue-restricted cAMP transcriptional response: SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes". The Journal of Biological Chemistry. 278 (46): 45224–30. doi:10.1074/jbc.M309036200. PMID12944398.
↑Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID19067971.
↑Das D, Kaur I, Ali MJ, Biswas NK, Das S, Kumar S, Honavar SG, Maitra A, Chakrabarti S, Majumder PP (Jul 2014). "Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma". Optometry and Vision Science. 91 (7): e185–92. doi:10.1097/OPX.0000000000000309. PMID24927141.
↑Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan WJ (July 2000). "Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3". Hum. Genet. 107 (1): 1–6. doi:10.1007/s004390000328. PMID10982026.
↑Bondurand N, Pingault V, Goerich DE, Lemort N, Le Caignec C, Wegner M, Goossens M (August 2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. doi:10.1093/hmg/9.13.1907. PMID10942418.
↑Lang D, Epstein JA (April 2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. doi:10.1093/hmg/ddg107. PMID12668617.
↑Ludwig A, Rehberg S, Wegner, M (January 2004). "Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors". FEBS Letters. 556 (1–3): 236–44. doi:10.1016/s0014-5793(03)01446-7. PMID14706856.
↑Li H, Lu Y, Smith HK, Richardson W (December 2007). "Olig1 and Sox10 Interact Synergistically to Drive Myelin Basic Protein Transcription in Oligodendrocytes". The Journal of Neuroscience. 27 (52): 14375–82. doi:10.1523/jneurosci.4456-07.2007. PMID18160645.
↑Bondurand N, Sham MH (October 2013). "The role of SOX10 during enteric nervous system development". Dev. Biol. 382 (1): 330–43. doi:10.1016/j.ydbio.2013.04.024. PMID23644063.
↑Schlierf B, Lang S, Kosian T, Werner T, Wegner M (November 2011). "The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi". J. Mol. Biol. 353 (5): 1033–42. doi:10.1016/j.jmb.2005.09.013. PMID16214168.
Further reading
Jacobs JM, Wilson J (1992). "An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome". Acta Neuropathol. 83 (6): 670–4. doi:10.1007/BF00299420. PMID1636383.
Southard-Smith EM, Kos L, Pavan WJ (1998). "Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model". Nat. Genet. 18 (1): 60–4. doi:10.1038/ng0198-60. PMID9425902.
Kuhlbrodt K, Schmidt C, Sock E, Pingault V, Bondurand N, Goossens M, Wegner M (1998). "Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients". J. Biol. Chem. 273 (36): 23033–8. doi:10.1074/jbc.273.36.23033. PMID9722528.
Pusch C, Hustert E, Pfeifer D, Südbeck P, Kist R, Roe B, Wang Z, Balling R, Blin N, Scherer G (1998). "The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor". Hum. Genet. 103 (2): 115–23. doi:10.1007/s004390050793. PMID9760192.
Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M (2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. doi:10.1093/hmg/9.13.1907. PMID10942418.
Smit DJ, Smith AG, Parsons PG, Muscat GE, Sturm RA (2000). "Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors". Eur. J. Biochem. 267 (21): 6413–22. doi:10.1046/j.1432-1327.2000.01737.x. PMID11029584.
Pingault V, Girard M, Bondurand N, Dorkins H, Van Maldergem L, Mowat D, Shimotake T, Verma I, Baumann C, Goossens M (2002). "SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism". Hum. Genet. 111 (2): 198–206. doi:10.1007/s00439-002-0765-8. PMID12189494.
Lang D, Epstein JA (2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. doi:10.1093/hmg/ddg107. PMID12668617.
Shimotake T, Tomiyama H, Aoi S, Iwai N (2003). "Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung's disease with reference to the type of RET/GDNF/SOX10 gene mutation". J. Pediatr. Surg. 38 (5): 698–701. doi:10.1016/jpsu.2003.50186. PMID12720173.
Chan KK, Wong CK, Lui VC, Tam PK, Sham MH (2003). "Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation". J. Cell. Biochem. 90 (3): 573–85. doi:10.1002/jcb.10656. PMID14523991.
Inoue K, Khajavi M, Ohyama T, Hirabayashi S, Wilson J, Reggin JD, Mancias P, Butler IJ, Wilkinson MF, Wegner M, Lupski JR (2004). "Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations". Nat. Genet. 36 (4): 361–9. doi:10.1038/ng1322. PMID15004559.