Affinage

SOX10

Transcription factor SOX-10 · UniProt P56693

Length
466 aa
Mass
49.9 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX10 is a dimerizing HMG-box transcription factor that governs the specification, survival, and differentiation of neural crest derivatives and their glial and melanocytic progeny (PMID:9425902, PMID:12691661). In neural crest stem cells it preserves multipotency and is required for induction of neurogenic factors MASH1 and PHOX2B, while its loss triggers apoptosis and depletion of peripheral nervous system and melanocyte lineages (PMID:9425902, PMID:12691661). SOX10 has little autonomous transactivation capacity and operates combinatorially, binding adjacent promoter/enhancer sites and acting synergistically with cell-type-specific partners through its N-terminal and central transactivation domains: Oct6/SCIP, Pax3 and Krox20 in glia (PMID:9412504), EGR2/Krox20 and the nuclear receptors NR2F1/NR2F2 at Schwann-cell myelin genes (PMID:18634568, PMID:25974668), Olig1 and the chromatin remodeler CHD7 at oligodendrocyte myelin enhancers (PMID:18160645, PMID:26928066), and Myrf, which both co-activates late myelination genes and sequesters SOX10 from earlier oligodendroglial targets (PMID:31828317). Its DNA-binding is cooperative and dimeric, requiring residues flanking the HMG domain; this dimerization is essential for full activation of the myelin protein zero (Mpz) promoter and for Schwann cells to enter the promyelinating stage, whereas a distinct central transactivation domain is uniquely needed for satellite glia and Schwann cell myelination (PMID:12490719, PMID:17699610). SOX10 directly activates an extended target repertoire including MITF, MBP, MIA, PMP2, S100B, MCM5, FOXD3, and the microRNAs miR335/miR338 (which reciprocally suppress Sox9) and miR-29a-3p, thereby controlling pigmentation, myelin gene programs, proliferation, and lineage stability (PMID:10973953, PMID:18160645, PMID:24608986, PMID:27955842, PMID:28370559, PMID:29295999, PMID:30506895, PMID:25536222, PMID:36919939). SOX10 activity is post-translationally tuned: ERK1/2 phosphorylation blocks sumoylation at K55 to dampen transcriptional output as part of an ERK/SOX10/FOXD3/ERBB3 axis driving RAF-inhibitor resistance, and Akt-dependent FoxO1 phosphorylation controls Sox10 promoter activity in the oligodendrocyte lineage (PMID:29295999, PMID:34385359). In disease, dominant-negative WS4-linked mutants repress MITF (PMID:10973953), SOX10 is a melanoma dependency whose loss induces senescence and engages a counter-regulatory SOX9 loop (PMID:22772081, PMID:23913827, PMID:25629959), and recurrent indel mutations that retain DNA binding but lose transactivation drive schwannoma by blocking glial differentiation (PMID:37436963).

Mechanistic history

Synthesis pass · year-by-year structured walk · 33 steps
  1. 1998 High

    Established that SOX10 is not an autonomous activator but a combinatorial transcriptional modulator, reframing how its glial gene control should be understood.

    Evidence Transcription and synergy assays with domain-deletion mutants and POU partner Tst-1/Oct6/SCIP in glial cells

    PMID:9412504

    Open questions at the time
    • Did not define the full set of synergistic partners
    • N-terminal interaction surface mapped only coarsely
  2. 1998 High

    Demonstrated that SOX10 is essential for neural crest derivative survival, establishing its developmental requirement in PNS formation.

    Evidence Dom premature-termination mutation in mice with in situ hybridization and apoptosis assays

    PMID:9425902

    Open questions at the time
    • Mechanistic basis of apoptosis not resolved
    • Relationship to Ednrb regulation correlative
  3. 2000 High

    Identified MITF as a direct SOX10 target and provided the molecular basis for WS4 pigmentation/deafness via dominant-negative mutant action.

    Evidence MITF promoter binding and activation assays plus dominant-negative WS4 mutant analysis and endogenous MITF measurement

    PMID:10973953

    Open questions at the time
    • Other WS4-relevant targets not addressed
    • Cofactor requirements at MITF promoter not defined
  4. 2002 High

    Defined the cooperative dimeric DNA-binding mode and showed it is required for full myelin gene activation, explaining a key biochemical feature of SOX10 function.

    Evidence Mutagenesis of residues flanking the HMG domain with DNA-binding and Mpz promoter assays

    PMID:12490719

    Open questions at the time
    • Structural model of the dimer not determined
    • In vivo requirement tested only later
  5. 2003 High

    Showed SOX10 maintains neural crest multipotency in a dosage-dependent manner, separating its stem-cell maintenance role from differentiation control.

    Evidence In vitro NCSC assays and in vivo gene-dosage genetics with MASH1/PHOX2B readouts

    PMID:12691661

    Open questions at the time
    • Direct targets mediating multipotency not identified
    • Dosage thresholds molecularly undefined
  6. 2005 Medium

    Demonstrated that long-range upstream enhancers are required for proper Sox10 expression, expanding the disease model beyond coding mutations.

    Evidence 15.9 kb upstream deletion mouse model with enhancer assays and expression analysis

    PMID:16330480

    Open questions at the time
    • Enhancer assignment partial
    • Trans-factors binding the enhancer not fully identified
  7. 2006 Medium

    Placed SOX10 in balanced cooperation with endothelin signaling for enteric and melanocyte development, implicating migration/survival rather than differentiation.

    Evidence Sox10;Ednrb and Sox10;Edn3 double-mutant mouse analysis with apoptosis/proliferation/differentiation readouts

    PMID:16650841

    Open questions at the time
    • Molecular link between SOX10 and endothelin signaling undefined
    • Direct transcriptional connection not shown
  8. 2007 High

    Separated SOX10 dimerization and central transactivation domains as functionally distinct, mapping which glial transitions each domain controls.

    Evidence Two hypomorphic Sox10 alleles (dimerization triple-alanine; central TAD deletion) analyzed in mice

    PMID:17699610

    Open questions at the time
    • Domain-specific cofactor partners not fully resolved
    • Direct targets per domain not enumerated
  9. 2007 High

    Established EGR2/SOX10 synergy at the Mpz gene and linked dominant EGR2 neuropathy mutations to disrupted synergy, providing a mechanistic disease readout.

    Evidence Reporter assays with binding-site mutagenesis and co-activation with Egr family members

    PMID:18634568

    Open questions at the time
    • Physical EGR2-SOX10 contact surface not mapped
    • Genome-wide co-targets defined only later
  10. 2008 High

    Identified Olig1 as a physical SOX10 partner activating mbp, revealing a CNS-specific cooperative module distinct from the Schwann-cell program.

    Evidence Physical association assays and mbp reporter assays with conserved motifs, zebrafish/mouse comparison

    PMID:18160645

    Open questions at the time
    • Species difference in Olig2 binding unexplained
    • Stoichiometry of the complex unknown
  11. 2012 High

    Established SOX10 as a melanoma dependency required for tumor formation and neural crest stem-cell properties, extending its developmental role to cancer.

    Evidence Sox10 haploinsufficiency in NRAS(Q61K) mouse model plus siRNA knockdown and in vivo tumor assays in human cells

    PMID:22772081

    Open questions at the time
    • Direct effector targets of the tumor phenotype not fully defined here
    • Mechanism of stem-cell property maintenance unresolved
  12. 2013 High

    Defined the cell-cycle consequences of SOX10 loss in melanoma (G1 arrest, senescence, p21/p27 induction, RB hypophosphorylation), connecting SOX10 to proliferative control.

    Evidence Stable shRNA knockdown with cell-cycle and western analyses plus Grm1(Tg) mouse model

    PMID:23913827

    Open questions at the time
    • Direct vs indirect regulation of cell-cycle effectors not separated
    • MITF dependence of the arrest not fully dissected
  13. 2013 Medium

    Linked SOX10 to enteric neural crest migration through β1-integrin regulation, framing a cell-adhesion/migration function.

    Evidence Sox10;Itgb1 double-mutant mice with video-microscopy of migration

    PMID:23608456

    Open questions at the time
    • Direct transcriptional regulation of Itgb1 not established
    • Genetic interaction may be indirect
  14. 2014 High

    Identified MIA as a direct SOX10 target mediating melanoma invasion, providing a functional rescue-validated invasion effector.

    Evidence EMSA, ChIP, luciferase, invasion assays with ectopic MIA rescue

    PMID:24608986

    Open questions at the time
    • Cofactors at the MIA promoter not defined
    • In vivo invasion contribution not tested
  15. 2014 High

    Established S100B as a direct SOX10 target through defined response elements, linking SOX10 to Schwann cell proliferation control and myelination.

    Evidence Promoter/intron deletion-mutation mapping, gain/loss-of-function, and DRG myelination co-culture

    PMID:25536222

    Open questions at the time
    • S100B downstream signaling in myelination not fully resolved
    • In vivo requirement not tested
  16. 2015 High

    Mapped SOX10 genome-wide enhancer occupancy in two glial lineages and identified lineage-specific co-regulators (Olig2/Myrf vs Egr2; NR2F1/2), unifying its cell-type-specific partnerships.

    Evidence In vivo ChIP-Seq in spinal cord and sciatic nerve with transcriptome profiling and siRNA validation

    PMID:25974668

    Open questions at the time
    • Direct vs cooperative binding contributions not parsed at all sites
    • NR2F1/2 contact with SOX10 not biochemically shown
  17. 2015 High

    Established a SOX10-SOX9 reciprocal feedback loop as the basis of the anti-tumorigenic effect of SOX10 loss in melanoma.

    Evidence SOX10 knockdown, SOX9 overexpression, ChIP of SOX9 at SOX10 promoter, in vivo epistasis

    PMID:25629959

    Open questions at the time
    • How SOX10 normally restrains SOX9 transcriptionally not fully defined
    • Generality across melanoma subtypes untested
  18. 2015 High

    Extended SOX10 function to mammary epithelial stem/progenitor competence downstream of FGF signaling, broadening its role beyond neural crest lineages.

    Evidence Conditional deletion and overexpression with mammary stem-cell and organoid assays

    PMID:26365194

    Open questions at the time
    • Direct SOX10 targets in mammary cells not identified
    • Mechanism of FGF-to-SOX10 coupling unresolved
  19. 2015 Medium

    Showed Ets1 activates a neural-crest Sox10 enhancer and interacts synergistically with Sox10, identifying an upstream regulatory input.

    Evidence Double-heterozygous mice, enhancer reporter assays, G102E mutation analysis

    PMID:25912689

    Open questions at the time
    • Direct Ets1-Sox10 protein interaction not demonstrated
    • Synergy mechanism molecularly undefined
  20. 2016 High

    Identified MCM5 as a direct SOX10 target linking SOX10 to DNA replication licensing and melanocyte proliferation.

    Evidence RNAi knockdown, ChIP at MCM5 promoter, reporter assays, MCM5 rescue

    PMID:27955842

    Open questions at the time
    • Other replication targets not surveyed
    • In vivo proliferation contribution untested
  21. 2016 High

    Established CHD7 as a SOX10 chromatin-remodeling partner at myelinogenic enhancers required for CNS myelination and remyelination.

    Evidence Genome-wide ChIP co-occupancy, transcriptome profiling, genetic mouse models

    PMID:26928066

    Open questions at the time
    • Biochemical SOX10-CHD7 contact not mapped
    • Remyelination mechanism not fully dissected
  22. 2017 High

    Revealed that SOX10 activates miR335/miR338 to post-transcriptionally suppress Sox9, formalizing an inverse Sox10-Sox9 coupling during oligodendrocyte differentiation.

    Evidence Sox10 deletion in oligodendroglia, miRNA profiling, 3'-UTR reporters, mathematical modeling

    PMID:28370559

    Open questions at the time
    • Direct vs indirect miRNA promoter activation not fully separated
    • In vivo necessity of the loop untested
  23. 2018 High

    Defined ERK1/2 phosphorylation as a switch that blocks K55 sumoylation to suppress SOX10 activity, and placed SOX10/FOXD3 in a RAF-inhibitor resistance axis.

    Evidence Phospho- and sumo-site mutagenesis, ChIP, kinase inhibitors, in vitro/in vivo knockdown

    PMID:29295999

    Open questions at the time
    • Stoichiometry of phospho-sumo crosstalk in vivo unquantified
    • Other sumoylation-dependent targets not surveyed
  24. 2018 High

    Identified PMP2 as a direct SOX10/EGR2 co-target promoting melanoma invasion, extending myelin-gene regulation into the tumor context.

    Evidence RNA-Seq after overexpression, ChIP, EMSA, luciferase, invasion assays

    PMID:30506895

    Open questions at the time
    • In vivo invasion role untested
    • Mechanism of PMP2-driven invasion undefined
  25. 2018 Medium

    Mapped additional SOX10 phosphosites (S24, S45, T240) affecting activity, localization, and stability, broadening the post-translational regulatory map.

    Evidence Mass spectrometry phosphoproteomics, site mutagenesis, activity/localization/stability assays

    PMID:29315345

    Open questions at the time
    • Limited functional depth per site
    • Responsible kinases not definitively assigned
  26. 2020 High

    Showed Myrf has a dual cooperative/sequestering relationship with SOX10, explaining how the same factor can both promote late and inhibit early oligodendroglial gene programs.

    Evidence ChIP-Seq, co-immunoprecipitation, reporter assays, Myrf binding-site mutagenesis

    PMID:31828317

    Open questions at the time
    • Structural basis of sequestration unknown
    • Quantitative balance between modes in vivo unresolved
  27. 2019 High

    Demonstrated SOX10 is required for exocrine gland epithelial KIT+FGFR2b+ progenitor maintenance and secretory differentiation, generalizing its progenitor-control function.

    Evidence Conditional deletion and overexpression with lineage tracing and organoids

    PMID:30713042

    Open questions at the time
    • Direct epithelial SOX10 targets not identified
    • FGFR2b-SOX10 coupling mechanism undefined
  28. 2021 High

    Identified an Akt-FoxO1 input controlling Sox10 promoter activity required for oligodendrocyte maturation, defining an upstream signaling control of SOX10 expression.

    Evidence Oligodendrocyte Akt1/2/3 triple knockout, FoxO1 phospho-site mutagenesis, ChIP at Sox10 promoter

    PMID:34385359

    Open questions at the time
    • How phospho-FoxO1 enables Sox10 transcription mechanistically unclear
    • Other Akt targets contributing not excluded
  29. 2021 Medium

    Linked SOX10 to immune evasion via a SOX10-IRF4-IRF1 axis regulating PD-L1 independently of JAK-STAT.

    Evidence Genetic and pharmacologic SOX10 loss with IRF4/IRF1 and PD-L1 readouts

    PMID:34728538

    Open questions at the time
    • Direct SOX10 binding to IRF4 regulatory elements not shown
    • In vivo immune relevance addressed separately
  30. 2021 Medium

    Showed SOX10 controls immune checkpoint proteins HVEM/CEACAM1 and CD8+ T-cell-dependent tumor growth, connecting SOX10 to anti-tumor immunity.

    Evidence Sox10 knockout in immune-competent/deficient mice with CD8+ depletion and checkpoint modulation

    PMID:34879275

    Open questions at the time
    • Direct transcriptional regulation of HVEM/CEACAM1 not demonstrated
    • Mechanism of immune coupling indirect
  31. 2021 High

    Identified an upstream peak5 enhancer with dimeric SoxE binding sites driving sox10 in neural crest and melanoma, linking enhancer regulation to pigment patterning and tumor chromatin state.

    Evidence ATAC-Seq, in vivo EGFP reporters, binding-site mutagenesis, endogenous locus deletion in zebrafish

    PMID:34099848

    Open questions at the time
    • Mammalian conservation of peak5 not established here
    • Trans-factors beyond SoxE not fully defined
  32. 2023 High

    Established that recurrent SOX10 indel mutations retain DNA binding but lose transactivation to block Schwann cell differentiation, defining a schwannoma driver mechanism.

    Evidence ChIP-Seq, EMSA, luciferase, RNA-Seq comparing wild-type and mutant SOX10 in fetal glial cells

    PMID:37436963

    Open questions at the time
    • Cofactor loss underlying transactivation defect not pinpointed
    • In vivo tumorigenesis from these alleles untested
  33. 2023 Medium

    Showed SOX10 binds the miR-29a-3p promoter to suppress ACSL4 and limit neuronal ferroptosis, extending SOX10 regulation to a neuroprotective miRNA axis.

    Evidence ChIP, dual-luciferase, miR-29a-3p gain/loss, ACSL4 and ferroptosis assays in an ICH model

    PMID:36919939

    Open questions at the time
    • Single-lab in vitro ICH model only
    • In vivo relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SOX10's combinatorial partner choice, dimeric binding, and post-translational modification state are integrated to select between progenitor-maintenance, myelination, and oncogenic gene programs in a given cell remains unresolved.
  • No unified model linking phospho/sumo state to partner selection
  • Structural basis of context-specific complexes undefined
  • Quantitative dosage thresholds across lineages not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 13 GO:0003677 DNA binding 8
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5
Partners
CHD7EGR2MYRFNR2F1OCT6/POU3F1OLIG1PAX3SOX9

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SOX10 functions as a transcriptional modulator in glial cells that lacks autonomous transcriptional activity but acts synergistically with the POU domain protein Tst-1/Oct6/SCIP; synergy depends on binding to adjacent sites in target promoters and is mediated by the N-terminal regions of both proteins. SOX10 also modulates the function of Pax3 and Krox-20. Functional transcription assays, promoter binding studies, synergy assays with deletion/domain mutants The Journal of neuroscience High 9412504
1998 Premature termination of SOX10 (Dom mutation) disrupts expression of both Sox10 and Ednrb in neural crest cells and causes loss of neural crest derivatives through apoptosis, establishing SOX10 as essential for peripheral nervous system development from the neural crest. Mouse genetic model (Dom mutation), in situ hybridization, apoptosis assays Nature genetics High 9425902
2000 SOX10 directly binds and activates transcription of the MITF promoter; a WS4-linked mutant form of SOX10 acts as a dominant-negative repressor of MITF expression and reduces endogenous MITF protein levels, providing a molecular basis for hypopigmentation and deafness in WS4. Promoter binding assays, transcriptional activation assays, dominant-negative mutant analysis, endogenous MITF protein measurement The Journal of biological chemistry High 10973953
2002 SOX10 binds DNA cooperatively as a dimer; specific amino acid residues immediately preceding the HMG domain are required for cooperative (dimeric) binding, which cooperates with the HMG domain in a manner dependent on determinants within the first two alpha-helices. Cooperative binding is essential for full activation of the myelin protein zero (Mpz) promoter. Mutagenesis of cooperative binding residues, DNA binding assays, promoter activation assays Nucleic acids research High 12490719
2003 SOX10 maintains multipotency of neural crest stem cells by preserving both glial and neuronal potential, is required in vivo for induction of neurogenic transcription factors MASH1 and PHOX2B, and simultaneously inhibits overt neuronal differentiation (requiring higher Sox10 gene dosage than multipotency maintenance). In vitro neural crest stem cell assays, in vivo genetic analysis, gene dosage experiments Neuron High 12691661
2007 SOX10 dimerization domain and a newly defined central transactivation domain have distinct roles: a functional dimerization domain is required for immature Schwann cells to enter the promyelinating stage, while the central transactivation domain is uniquely required for satellite glia differentiation and Schwann cell myelination but not for early neural crest or oligodendrocyte differentiation. Hypomorphic Sox10 alleles (triple alanine substitution in dimerization domain; deletion of central transactivation domain) in mice, phenotypic analysis Development (Cambridge, England) High 17699610
2007 SOX10 and EGR2/Krox20 interact synergistically to activate the myelin protein zero (Mpz) gene; activation of the Mpz intronic element by Egr2 requires both Sox10-binding sites; Egr1 and Egr3 also cooperate with Sox10 at this element. Dominant EGR2 neuropathy mutations disrupt EGR2/SOX10 synergy. Reporter assays, mutagenesis of binding sites, co-activation assays with Egr family members Neuron glia biology High 18634568
2007 Olig1 physically associates with Sox10, and the Olig1/Sox10 complex activates myelin basic protein (mbp) transcription via conserved DNA sequence motifs in the mbp promoter region. In contrast, Olig2 does not bind Sox10 in zebrafish (though both OLIG1 and OLIG2 bind SOX10 in mouse). Physical binding assay (association), transcriptional reporter assays with conserved mbp promoter motifs, zebrafish and mouse comparison The Journal of neuroscience High 18160645
2012 SOX10 haploinsufficiency counteracts NRAS(Q61K)-driven congenital naevus and melanoma formation in vivo; SOX10 silencing in human melanoma cells suppresses neural crest stem cell properties, inhibits proliferation and cell survival, and abolishes tumor formation in vivo. Sox10 haploinsufficiency in genetic melanoma mouse model, SOX10 siRNA knockdown in human melanoma cells, in vivo tumor formation assays Nature cell biology High 22772081
2013 Stable SOX10 knockdown in human melanoma cells causes G1 cell cycle arrest, induces senescence, reduces MITF expression, elevates p21WAF1 and p27KIP2, leads to hypophosphorylated RB, and reduces E2F1 levels. SOX10 haploinsufficiency also reduces melanoma initiation in the Grm1(Tg) transgenic mouse model. Stable SOX10 shRNA knockdown, cell cycle analysis, western blotting, mouse genetic model Cancer research High 23913827
2014 SOX10 directly binds and activates the MIA (melanoma inhibitory activity) promoter, as demonstrated by EMSA and ChIP; SOX10 inhibition reduces MIA expression and promoter activity, and ectopic MIA restores the invasion capacity of SOX10-inhibited melanoma cells, establishing MIA as a direct SOX10 target mediating invasion. RNA interference, EMSA, chromatin immunoprecipitation, luciferase reporter assays, invasion assays, rescue with ectopic MIA The Journal of investigative dermatology High 24608986
2015 SOX9 is upregulated upon SOX10 loss in melanoma cells; SOX9 overexpression causes cell cycle arrest and apoptosis; SOX9 binds the SOX10 promoter and induces SOX10 downregulation, creating a feedback loop. SOX9 is required in vitro and in vivo for the anti-tumorigenic effect of SOX10 reduction. SOX10 knockdown, SOX9 overexpression, ChIP of SOX9 at SOX10 promoter, in vitro and in vivo tumor assays, epistasis experiments PLoS genetics High 25629959
2015 Sox10 is specifically expressed in mammary cells with the highest stem/progenitor activity; its deletion reduces stem/progenitor competence whereas overexpression increases stem/progenitor activity and causes a mesenchymal transition in mammary cells. SOX10 acts downstream of FGF signaling. Conditional Sox10 deletion, Sox10 overexpression, mammary stem cell functional assays, organoid assays Cell reports High 26365194
2015 SOX10 occupies genomic sites overlapping with active enhancers in both oligodendrocytes and Schwann cells; in oligodendrocytes, SOX10 binding sites co-occur with Olig2 and Myrf; in Schwann cells, SOX10 co-occupies sites with Egr2/Krox20. siRNA knockdown of nuclear receptors Nr2f1 and Nr2f2 reduces myelin gene expression (Mbp, Ndrg1) in Schwann cells, identifying them as SOX10 co-regulators. In vivo ChIP-Seq in spinal cord and sciatic nerve, transcriptome profiling, siRNA knockdown Glia High 25974668
2016 CHD7 interacts with SOX10 and together they target enhancers of key myelinogenic genes; Chd7 is required for proper onset of CNS myelination and remyelination. Genome-wide occupancy analysis (ChIP), transcriptome profiling, genetic mouse models Nature neuroscience High 26928066
2016 Sox10 directly activates the DNA replication licensing factor MCM5 by binding to conserved SOX10 consensus sequences in the MCM5 promoter; MCM5 overexpression partially rescues the proliferation defect caused by Sox10 knockdown in melanocytes. Sox10 knockdown (RNAi), ChIP of SOX10 at MCM5 promoter, promoter reporter assays, MCM5 rescue experiments Journal of dermatological science High 27955842
2017 SOX10 transcriptionally activates miR335 and miR338, which in turn recognize the 3'-UTR of Sox9 mRNA to reduce Sox9 protein levels post-transcriptionally in oligodendrocytes, creating an inverse coupling between Sox10 and Sox9 levels during oligodendrocyte differentiation. Sox10 deletion in oligodendroglial cells, miRNA expression analysis, 3'-UTR reporter assays, mathematical modeling Glia High 28370559
2018 ERK1/2-mediated phosphorylation of SOX10 inhibits its transcriptional activity by interfering with sumoylation of SOX10 at K55, which is essential for its transcription activity. SOX10 activates FOXD3 transcription by binding a regulatory element in the FOXD3 promoter, completing an ERK1/2/SOX10/FOXD3/ERBB3 axis mediating adaptive resistance to RAF inhibitors. Phosphorylation site mutagenesis, sumoylation assays, ChIP and promoter binding assays, kinase inhibitor experiments, in vitro and in vivo knockdown Nature communications High 29295999
2018 SOX10 directly regulates PMP2 (peripheral myelin protein 2), shown by ChIP, EMSA, and luciferase reporter assays; coregulation of PMP2 by SOX10 and EGR2 in melanoma cells was found; PMP2 expression increases melanoma cell invasion. RNA sequencing after SOX10 overexpression, ChIP, EMSA, luciferase reporter assays, invasion assays Pigment cell & melanoma research High 30506895
2018 SOX10 phosphorylation sites S24, S45, and T240 (within MAPK/CDK binding motifs) were identified by mass spectrometry and shown to affect SOX10 transcriptional activation on target promoters, subcellular localization, and protein stability in melanoma cells. Mass spectrometry phosphoproteomics, site-directed mutagenesis, transcriptional activation assays, subcellular localization imaging, protein stability assays PloS one Medium 29315345
2019 Sox10 is essential for maintenance and differentiation of epithelial KIT+FGFR2b+ progenitors into secretory units (acinar, myoepithelial, and intercalated duct cells) in exocrine glands; genetic deletion of epithelial Sox10 leads to loss of secretory units; Sox10 overexpression in ductal progenitors enhances plasticity toward KIT+ progenitors and secretory unit differentiation. Genetic conditional deletion of Sox10 in epithelial cells, Sox10 overexpression, lineage tracing, organoid assays Stem cell reports High 30713042
2020 Myrf cooperates with Sox10 to induce genes required for oligodendrocyte differentiation and myelin formation through joint binding to the same regulatory regions; Myrf also inhibits Sox10 activity on earlier oligodendroglial genes through physical interaction with Sox10 followed by sequestration (on genes lacking Myrf binding sites). ChIP-Seq for binding site characterization, co-immunoprecipitation/physical interaction assays, transcriptional reporter assays, mutagenesis of Myrf DNA-binding sites Nucleic acids research High 31828317
2021 Akt phosphorylates FoxO1, and phosphorylated FoxO1 is required for Sox10 promoter activity; Akt triple knockout in oligodendrocyte lineage cells causes complete loss of mature oligodendrocytes with downregulation of Sox10, and mutant FoxO1 without Akt phosphorylation epitopes is enriched at the Sox10 promoter. Oligodendrocyte-specific Akt1/2/3 triple conditional knockout mice, FoxO1 phospho-site mutagenesis, Sox10 promoter activity assays, ChIP of FoxO1 at Sox10 promoter The Journal of neuroscience High 34385359
2021 SOX10 represses IRF1 transcription via direct induction of the negative regulator IRF4, establishing a SOX10-IRF4-IRF1 axis that regulates PD-L1 expression independently of the JAK-STAT pathway in melanoma cells. Genetic and pharmacologic SOX10 loss-of-function, IRF4 and IRF1 expression analysis, PD-L1 regulation assays Cancer research Medium 34728538
2021 SOX10 positively regulates HVEM and CEACAM1 expression in melanoma; Sox10 knockout reduces tumor growth in immune-competent models in a manner dependent partly on CD8+ T cells, demonstrating that SOX10 controls immune checkpoint protein expression and anti-tumor immunity. Sox10 knockout mouse models (immune-competent and immune-deficient), CD8+ T cell depletion, CEACAM1 and HVEM expression modulation Cell reports Medium 34879275
2023 Recurrent in-frame insertion/deletion mutations in SOX10 found in schwannomas retain DNA binding capacity but have impaired transactivation of glial differentiation and myelination gene programs, driving schwannoma formation by impeding Schwann cell differentiation. ChIP-Seq, EMSA, luciferase reporter assays, RNA sequencing in fetal glial cells transduced with wild-type and mutant SOX10 Neuro-oncology High 37436963
2013 SOX10 modulates expression of β1-integrins (Itgb1) in enteric neural crest cells; double mutants for Sox10 and beta1-integrin show increased intestinal aganglionosis and impaired enteric neural crest cell migration with reduced speed and altered directionality, indicating SOX10 mediates enteric neural crest cell adhesion and migration through β1-integrin regulation. Genetic double mutant mouse analysis, video-microscopy of cell migration, β1-integrin expression analysis upon SOX10 modulation Developmental biology Medium 23608456
2014 SOX10 directly activates the S100B promoter through three core response elements with SOX motifs in the S100B promoter and intron 1; SOX10 knockdown suppresses S100B expression and enhances Schwann cell proliferation; S100B knockdown impairs myelination in dorsal root ganglia co-cultures. SOX10 overexpression/knockdown, promoter deletion/mutation analysis identifying SOX10 response elements, shRNA knockdown of S100B, DRG myelination assay PloS one High 25536222
2023 SOX10 binds the miR-29a-3p promoter region to increase miR-29a-3p expression; miR-29a-3p in turn targets and limits ACSL4 transcription, thereby inhibiting ferroptosis of hippocampal neurons in an ICH model. ChIP assay, dual-luciferase reporter assays, miR-29a-3p overexpression/knockdown, ACSL4 expression analysis, ferroptosis assays Journal of neurophysiology Medium 36919939
2006 Genetic interaction analysis of Sox10 with Ednrb and Edn3 double mutant mice shows that balanced Sox10 and endothelin signaling is required for normal ENS and melanocyte development; partial loss of Ednrb in Sox10 heterozygous mice impairs colonisation of the gut by enteric crest cells without increasing apoptosis or altering differentiation, indicating a migration/survival role. Sox10;Ednrb and Sox10;Edn3 double mutant mouse phenotype analysis, apoptosis assays, cell proliferation assays, differentiation marker analysis Developmental biology Medium 16650841
2005 A 15.9 kb deletion 47.3 kb upstream of Sox10 removes conserved non-coding sequences with strong enhancer potential in melanocytes and reduces Sox10 expression in vivo, causing an enteric aganglionosis and melanocyte loss phenotype (WS4-like), establishing that long-range regulatory elements are required for Sox10 expression. Comparative genomic sequence analysis, in vitro enhancer assay in melanocytes, transgene-insertion mouse model with Sox10 expression analysis Human molecular genetics Medium 16330480
2021 In vivo ATAC-Seq of zebrafish melanoma tumors identified recurrently open chromatin domains as sox10 enhancers; a conserved ~200 bp region 23 kb upstream of sox10 (peak5) containing dimeric SoxE/Sox10 binding sites drives expression in neural crest and melanoma; deletion of the endogenous peak5 locus decreases embryonic sox10 expression and disrupts adult stripe patterning. ATAC-Seq, EGFP reporter assays in vivo, binding site mutagenesis, endogenous locus deletion in zebrafish Communications biology High 34099848
2015 Ets1 activates an enhancer critical for Sox10 expression in neural crest-derived structures; this activation is inhibited by the variable spotting Ets1 G102E mutation; Ets1 and Sox10 interact synergistically in melanocyte and enteric ganglia development (double heterozygotes show greater hypopigmentation than additive effects of single heterozygotes). Genetic epistasis (double heterozygous mice), enhancer reporter assays, mutation analysis Developmental biology Medium 25912689

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Sox10, a novel transcriptional modulator in glial cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 646 9412504
1998 Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nature genetics 625 9425902
2003 SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron 461 12691661
2008 Sox10: a pan-schwannian and melanocytic marker. The American journal of surgical pathology 288 18636017
2012 Sox10 and S100 in the diagnosis of soft-tissue neoplasms. Applied immunohistochemistry & molecular morphology : AIMM 242 22495377
2012 Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma. Nature cell biology 221 22772081
2007 Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. American journal of human genetics 211 17999358
2006 Sorting out Sox10 functions in neural crest development. BioEssays : news and reviews in molecular, cellular and developmental biology 195 16927299
2005 DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia. The Journal of neuroscience : the official journal of the Society for Neuroscience 186 15930386
2016 Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination. Nature neuroscience 149 26928066
2000 Direct regulation of the Microphthalmia promoter by Sox10 links Waardenburg-Shah syndrome (WS4)-associated hypopigmentation and deafness to WS2. The Journal of biological chemistry 145 10973953
2007 Olig1 and Sox10 interact synergistically to drive myelin basic protein transcription in oligodendrocytes. The Journal of neuroscience : the official journal of the Society for Neuroscience 143 18160645
1999 The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4) syndrome. Genome research 123 10077527
2013 SOX10 expression in malignant melanoma, carcinoma, and normal tissues. Applied immunohistochemistry & molecular morphology : AIMM 112 23197006
2006 Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development. Developmental biology 105 16650841
2015 Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells. Cell reports 100 26365194
1998 Expression of the SOX10 gene during human development. FEBS letters 95 9720918
2015 Differential Sox10 genomic occupancy in myelinating glia. Glia 93 25974668
2013 The role of SOX10 during enteric nervous system development. Developmental biology 86 23644063
2021 SOX10: 20 years of phenotypic plurality and current understanding of its developmental function. Journal of medical genetics 82 34667088
2007 Hypomorphic Sox10 alleles reveal novel protein functions and unravel developmental differences in glial lineages. Development (Cambridge, England) 82 17699610
2020 Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype. Nature communications 81 33339831
2015 Antagonistic cross-regulation between Sox9 and Sox10 controls an anti-tumorigenic program in melanoma. PLoS genetics 81 25629959
2013 SOX10 ablation arrests cell cycle, induces senescence, and suppresses melanomagenesis. Cancer research 79 23913827
2014 SOX10 promotes melanoma cell invasion by regulating melanoma inhibitory activity. The Journal of investigative dermatology 74 24608986
2022 Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma. Nature communications 73 35296667
2021 Using the lineage determinants Olig2 and Sox10 to explore transcriptional regulation of oligodendrocyte development. Developmental neurobiology 73 34480425
2009 Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation. Development (Cambridge, England) 71 19570850
2018 Disparate effects of DOM extracted from coastal seawaters and freshwaters on photodegradation of 2,4-Dihydroxybenzophenone. Water research 70 30616040
2013 Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas. British journal of cancer 67 23799842
2022 TRPS1, GATA3, and SOX10 expression in triple-negative breast carcinoma. Human pathology 65 35413381
2018 ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma. Nature communications 65 29295999
2007 Interactions of Sox10 and Egr2 in myelin gene regulation. Neuron glia biology 65 18634568
2018 UBE2N Promotes Melanoma Growth via MEK/FRA1/SOX10 Signaling. Cancer research 64 30224375
2005 Co-expression of SOX9 and SOX10 during melanocytic differentiation in vitro. Experimental cell research 59 15896776
2005 Deletion of long-range sequences at Sox10 compromises developmental expression in a mouse model of Waardenburg-Shah (WS4) syndrome. Human molecular genetics 58 16330480
2002 Cooperative binding of Sox10 to DNA: requirements and consequences. Nucleic acids research 58 12490719
2019 The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor. PLoS genetics 57 31881017
2010 Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma. Experimental dermatology 53 19845757
2000 Expression of the Sox10 gene during mouse inner ear development. Brain research. Molecular brain research 51 11113541
2021 SOX10 Regulates Melanoma Immunogenicity through an IRF4-IRF1 Axis. Cancer research 49 34728538
2019 Sox10 Regulates Plasticity of Epithelial Progenitors toward Secretory Units of Exocrine Glands. Stem cell reports 49 30713042
2017 Transcription factor Sox10 regulates oligodendroglial Sox9 levels via microRNAs. Glia 48 28370559
2020 Myrf guides target gene selection of transcription factor Sox10 during oligodendroglial development. Nucleic acids research 46 31828317
2002 Expression of Sox8, Sox9 and Sox10 in the developing valves and autonomic nerves of the embryonic heart. Mechanisms of development 46 12351187
2014 SOX10 transactivates S100B to suppress Schwann cell proliferation and to promote myelination. PloS one 45 25536222
2006 Expression of SOX9 and SOX10 in central neuroepithelial tumor. Journal of neuro-oncology 44 16791471
2010 PAX3 and SOX10 activate MET receptor expression in melanoma. Pigment cell & melanoma research 43 20067553
2008 SOX9 and SOX10 but not BRN2 are required for nestin expression in human melanoma cells. The Journal of investigative dermatology 40 18923447
2014 SOX10 is a novel oncogene in hepatocellular carcinoma through Wnt/β-catenin/TCF4 cascade. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 39 25001176
2020 CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR-637 and up-regulating SOX10. Molecular oncology 37 33085838
2016 SOX10-MITF pathway activity in melanoma cells. Archives of medical science : AMS 36 29181082
2013 Value of SOX10 immunostaining in tumor diagnosis. Advances in anatomic pathology 35 23752089
2021 SOX10 requirement for melanoma tumor growth is due, in part, to immune-mediated effects. Cell reports 32 34879275
2018 Identification and functional analysis of SOX10 phosphorylation sites in melanoma. PloS one 32 29315345
2018 SOX10 Immunoexpression in Basaloid Squamous Cell Carcinomas: A Diagnostic Pitfall for Ruling out Salivary Differentiation. Head and neck pathology 31 30498968
2017 SOX10 induced Nestin expression regulates cancer stem cell properties of TNBC cells. Biochemical and biophysical research communications 31 28189679
2023 Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs. Neuro-oncology 30 37436963
2021 Akt Regulates Sox10 Expression to Control Oligodendrocyte Differentiation via Phosphorylating FoxO1. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 34385359
2013 Sox appeal - Sox10 attracts epigenetic and transcriptional regulators in myelinating glia. Biological chemistry 30 23729567
2010 SOX10 expression in superficial spreading and nodular malignant melanomas. Melanoma research 30 20890226
2021 SOX10 ablation severely impairs the generation of postmigratory neural crest from human pluripotent stem cells. Cell death & disease 28 34453037
2022 SOX9 and SOX10 control fluid homeostasis in the inner ear for hearing through independent and cooperative mechanisms. Proceedings of the National Academy of Sciences of the United States of America 27 36343245
2009 Oligodendroglial and pan-neural crest expression of Cre recombinase directed by Sox10 enhancer. Genesis (New York, N.Y. : 2000) 27 19830815
2023 Molecular insights into effects of PBAT microplastics on latosol microbial diversity and DOM chemodiversity. Journal of hazardous materials 26 36848842
2019 Combined use of SOX10 and GATA3 in mammary carcinoma. Pathology, research and practice 26 31924335
2013 Sox10 and Itgb1 interaction in enteric neural crest cell migration. Developmental biology 26 23608456
2007 Progesterone derivatives increase expression of Krox-20 and Sox-10 in rat Schwann cells. Journal of molecular neuroscience : MN 26 17478888
2020 Immunohistological Expression of SOX-10 in Triple-Negative Breast Cancer: A Descriptive Analysis of 113 Samples. International journal of molecular sciences 25 32899175
2023 Clinical Significance of SOX10 Expression in Human Pathology. Current issues in molecular biology 24 38132479
2017 MYB, CD117 and SOX-10 expression in cutaneous adnexal tumors. Journal of cutaneous pathology 23 28098399
2017 Sox10+ Cells Contribute to Vascular Development in Multiple Organs-Brief Report. Arteriosclerosis, thrombosis, and vascular biology 23 28751573
2014 SOX10 mutations mimic isolated hearing loss. Clinical genetics 23 25256313
2021 DNA-stable isotope probing (DNA-SIP) identifies marine sponge-associated bacteria actively utilizing dissolved organic matter (DOM). Environmental microbiology 22 34159693
2018 The miR-31-SOX10 axis regulates tumor growth and chemotherapy resistance of melanoma via PI3K/AKT pathway. Biochemical and biophysical research communications 22 29969627
2018 PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms. Journal of pathology and translational medicine 22 30424592
2018 The myelin protein PMP2 is regulated by SOX10 and drives melanoma cell invasion. Pigment cell & melanoma research 22 30506895
2014 SOX-10 expression in cutaneous myoepitheliomas and mixed tumors. Journal of cutaneous pathology 22 24329979
2019 SOX10 expression in mammary invasive ductal carcinomas and benign breast tissue. Virchows Archiv : an international journal of pathology 21 30903273
2019 SOX-10 staining in dermal scars. Journal of cutaneous pathology 21 30950082
2017 Sox10 and DOG1 Expression in Primary Adnexal Tumors of the Skin. The American Journal of dermatopathology 21 28394798
2018 Key Genes and Pathways Associated With Inner Ear Malformation in SOX10  Mutation Pigs. Frontiers in molecular neuroscience 20 29922125
2017 Sox10+ adult stem cells contribute to biomaterial encapsulation and microvascularization. Scientific reports 20 28071739
2016 Sox10 regulates skin melanocyte proliferation by activating the DNA replication licensing factor MCM5. Journal of dermatological science 19 27955842
2024 Spatial gradients and molecular transformations of DOM, DON and DOS in human-impacted estuarine sediments. Environment international 17 38430584
2023 Targeting Upregulated cIAP2 in SOX10-Deficient Drug Tolerant Melanoma. Molecular cancer therapeutics 17 37343247
2021 Functional in vivo characterization of sox10 enhancers in neural crest and melanoma development. Communications biology 17 34099848
2017 SOX10 immunohistochemistry in sweat ductal/glandular neoplasms. Journal of cutaneous pathology 17 28343365
2016 Can SOX-10 or KBA.62 Replace S100 Protein in Immunohistochemical Evaluation of Sentinel Lymph Nodes for Metastatic Melanoma? Applied immunohistochemistry & molecular morphology : AIMM 17 25611246
2012 Expression of Sox10 and c-kit in sinonasal mucosal melanomas arising in the Chinese population. Head and neck pathology 17 22736149
2023 SOX10. Journal of clinical pathology 16 37336549
2020 Novel SOX10 Mutations in Waardenburg Syndrome: Functional Characterization and Genotype-Phenotype Analysis. Frontiers in genetics 16 33362852
2019 SOX10 and GATA3 in Adenoid Cystic Carcinoma and Polymorphous Adenocarcinoma. Head and neck pathology 16 31222589
2015 Sox10 is superior to S100 in the diagnosis of meningioma. Applied immunohistochemistry & molecular morphology : AIMM 16 25265429
2015 The transcription factors Ets1 and Sox10 interact during murine melanocyte development. Developmental biology 16 25912689
2023 Mechanism of SOX10 in ferroptosis of hippocampal neurons after intracerebral hemorrhage via the miR-29a-3p/ACSL4 axis. Journal of neurophysiology 15 36919939
2022 Dissolved organic matter (DOM) was detected in MSWI plant: An investigation of DOM and potential toxic elements variation in the bottom ash and fly ash. The Science of the total environment 15 35257758
2020 Conjunctival nevi and melanoma: multiparametric immunohistochemical analysis, including p16, SOX10, HMB45, and Ki-67. Human pathology 15 32707054
2022 Comparative role of SOX10 gene in the gliogenesis of central, peripheral, and enteric nervous systems. Differentiation; research in biological diversity 14 36198237
2021 SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma. Life (Basel, Switzerland) 14 33801642

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