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Sox10 Cooperates with the Mediator Subunit 12 During Terminal Differentiation of Myelinating Glia

Overview
Journal J Neurosci
Specialty Neurology
Date 2013 Apr 12
PMID 23575864
Citations 30
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Abstract

Several transcription factors are essential for terminal differentiation of myelinating glia, among them the high-mobility-group-domain-containing protein Sox10. To better understand how these factors exert their effects and shape glial expression programs, we identified and characterized a physical and functional link between Sox10 and the Med12 subunit of the Mediator complex that serves as a conserved multiprotein interphase between transcription factors and the general transcription machinery. We found that Sox10 bound with two of its conserved domains to the C-terminal region of Med12 and its close relative, Med12-like. In contrast to Med12-like, substantial amounts of Med12 were detected in both Schwann cells and oligodendrocytes. Its conditional glia-specific deletion in mice led to terminal differentiation defects that were highly reminiscent of those obtained after Sox10 deletion. In support of a functional cooperation, both proteins were jointly required for Krox20 induction and were physically associated with the critical regulatory region of the Krox20 gene in myelinating Schwann cells. We conclude that Sox10 functions during terminal differentiation of myelinating glia, at least in part by Med12-dependent recruitment of the Mediator complex.

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References
1.
Stolt C, Lommes P, Sock E, Chaboissier M, Schedl A, Wegner M . The Sox9 transcription factor determines glial fate choice in the developing spinal cord. Genes Dev. 2003; 17(13):1677-89. PMC: 196138. DOI: 10.1101/gad.259003. View

2.
Wissmuller S, Kosian T, Wolf M, Finzsch M, Wegner M . The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors. Nucleic Acids Res. 2006; 34(6):1735-44. PMC: 1421504. DOI: 10.1093/nar/gkl105. View

3.
Finzsch M, Schreiner S, Kichko T, Reeh P, Tamm E, Bosl M . Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage. J Cell Biol. 2010; 189(4):701-12. PMC: 2872908. DOI: 10.1083/jcb.200912142. View

4.
Jagalur N, Ghazvini M, Mandemakers W, Driegen S, Maas A, Jones E . Functional dissection of the Oct6 Schwann cell enhancer reveals an essential role for dimeric Sox10 binding. J Neurosci. 2011; 31(23):8585-94. PMC: 3137940. DOI: 10.1523/JNEUROSCI.0659-11.2011. View

5.
Qi Y, Cai J, Wu Y, Wu R, Lee J, Fu H . Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development. 2001; 128(14):2723-33. DOI: 10.1242/dev.128.14.2723. View