Affinage

SOX10

Transcription factor SOX-10 · UniProt P56693

Length
466 aa
Mass
49.9 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX10 is an HMG-box transcription factor that serves as a master regulator of neural crest cell fate specification, glial differentiation, myelination, and melanocyte biology. It binds DNA as a monomer or cooperative dimer—dimeric binding requiring an N-terminal dimerization domain and paired heptameric sites—and activates lineage-specific gene programs including MITF (synergistically with PAX3), ErbB3, MPZ, MBP, Dhh, S100B, FOXD3, and MIA by partnering with cofactors such as Egr2, Olig1, Chd7, Myrf, and the BRG1 chromatin remodeler (PMID:10931919, PMID:10942418, PMID:18634568, PMID:26928066, PMID:31828317, PMID:28431046). Its transcriptional activity is positively regulated by sumoylation at K55 and negatively regulated by ERK-mediated phosphorylation, and distinct transactivation domains are deployed at sequential stages of Schwann cell and oligodendrocyte differentiation (PMID:29295999, PMID:17699610). SOX10 haploinsufficiency causes Waardenburg–Hirschsprung disease through loss of enteric ganglia and melanocytes (PMID:9425902, PMID:9722528), and SOX10 is required for melanoma cell proliferation, survival, and invasion, acting through MITF-dependent cell-cycle control and the SOX10→MIA invasion axis (PMID:22772081, PMID:23913827, PMID:24608986).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Positional cloning of the Dom locus identified SOX10 as the transcription factor essential for peripheral nervous system development and neural crest survival, establishing the gene's foundational role.

    Evidence Positional cloning and sequencing of Dom mouse, in situ hybridization, apoptosis assays in mutant embryos; corroborated by independent mapping and truncated-protein inactivation assays

    PMID:9425902 PMID:9560246 PMID:9722528

    Open questions at the time
    • Precise transcriptional targets downstream of SOX10 in enteric precursors were not defined
    • Mechanism by which truncated SOX10 acts dominant-negatively was not resolved
  2. 2000 High

    Biochemical characterization revealed that SOX10 operates through monomeric and cooperative dimeric DNA-binding modes with distinct kinetic properties, and that it directly activates MITF in synergy with PAX3, linking SOX10 to melanocyte specification.

    Evidence EMSA, footprinting, DNA bending analysis for binding modes; MITF promoter-reporter assays, co-transfection with PAX3, Western blot for endogenous MITF

    PMID:10931919 PMID:10942418 PMID:10973953

    Open questions at the time
    • Structural basis of the SOX10–PAX3 interaction was not determined
    • Whether dimeric versus monomeric binding governs different target gene sets in vivo was unknown
  3. 2001 High

    Loss-of-function studies in mouse and zebrafish demonstrated that SOX10 is required for differentiation of peripheral glia and melanocytes, controls ErbB3 and mitf expression, and that its role is conserved across vertebrates.

    Evidence Sox10 knockout mice (ErbB3 expression analysis), zebrafish colourless/sox10 mutant with single-cell fate mapping and rescue by ectopic sox10

    PMID:11156606 PMID:11684650

    Open questions at the time
    • Whether SOX10 directly binds ErbB3 regulatory elements was not shown
    • Mechanism of SOX10 dose-dependent effects on different NCC lineages was unresolved
  4. 2003 High

    SOX10 was shown to maintain neural crest stem cell multipotency in a dose-dependent manner—lower doses sustain neurogenic potential while higher doses inhibit overt neuronal differentiation—establishing SOX10 as a gatekeeper of lineage choice.

    Evidence In vitro NCSC culture with retroviral overexpression and loss-of-function analysis in Sox10 mutant embryos

    PMID:12691661

    Open questions at the time
    • Molecular targets mediating the dose-dependent switch were not identified
    • How SOX10 inhibits neuronal differentiation mechanistically was unclear
  5. 2004 High

    The discovery that Sox10 is required for oligodendrocyte terminal differentiation and can form heterodimers with Sox8 on shared response elements extended SOX10 function from PNS to CNS glia.

    Evidence Sox8/Sox10 double-mutant mice, EMSA for Sox8 on Sox10 elements, heterodimerization assays, reporter assays

    PMID:15102707

    Open questions at the time
    • Whether Sox8/Sox10 heterodimers versus homodimers activate distinct gene sets in vivo was not resolved
    • Genome-wide target overlap was not assessed
  6. 2007 High

    Domain-function studies using hypomorphic alleles dissected SOX10's modular architecture: the dimerization domain is required for the immature-to-promyelinating Schwann cell transition, a central transactivation domain for satellite glia and myelination, and Olig1 partners with Sox10 to activate MBP in oligodendrocytes.

    Evidence Hypomorphic Sox10 mouse alleles with specific domain mutations; co-IP of Olig1–Sox10, mbp promoter reporter assays with binding-site mutagenesis

    PMID:17699610 PMID:18160645

    Open questions at the time
    • How the central transactivation domain recruits coactivators was unknown
    • Whether Olig1–Sox10 interaction is direct or bridged was not fully resolved
  7. 2007 High

    Identification of composite Egr2/Sox10 regulatory modules at multiple myelin gene loci (MPZ, MAG, MBP, periaxin) established a general co-regulatory logic for peripheral myelination.

    Evidence Reporter assays with Sox10-site mutagenesis, ChIP, co-transfection with Egr family members, computational module identification

    PMID:18634568

    Open questions at the time
    • Temporal sequence of Egr2 and Sox10 occupancy during myelination onset was not resolved
    • In vivo necessity of individual composite elements was not tested
  8. 2011 High

    In vivo transgenic enhancer assays proved that dimeric—not monomeric—Sox10 binding to paired sites in the Oct6 Schwann cell enhancer is essential for enhancer activity, establishing a feed-forward circuit (Sox10→Oct6→Krox20) timing myelination onset.

    Evidence Transgenic mouse enhancer assays with mutagenesis of Sox binding sites in Oct6 SCE

    PMID:21653862

    Open questions at the time
    • How Sox10 cooperates with other factors at the Oct6 SCE was not defined
    • Chromatin state changes at the SCE during Schwann cell development were not characterized
  9. 2012 High

    Conditional deletion revealed that Sox10 activates Dhh in Schwann cells to non-cell-autonomously promote perineurial sheath formation, and separately, that Sox10 haploinsufficiency suppresses melanoma in two independent mouse models.

    Evidence Sox10 conditional KO in Schwann cells with Dhh enhancer reporter and in vivo assays; Nras(Q61K)/Sox10+/- genetic epistasis and human melanoma xenograft with SOX10 RNAi

    PMID:22514309 PMID:22772081

    Open questions at the time
    • Whether SOX10's pro-tumorigenic role is solely MITF-dependent or involves additional pathways was not fully resolved
    • Non-cell-autonomous Dhh signaling mechanism to perineurium was not dissected
  10. 2013 High

    Mechanistic dissection showed SOX10 sustains melanoma proliferation by maintaining MITF levels, suppressing p21/p27, and keeping RB phosphorylated, directly linking SOX10 to cell-cycle control.

    Evidence Stable SOX10 shRNA in melanoma cells, cell-cycle analysis, Western blotting for p21, p27, RB, E2F1; Grm1(Tg) mouse melanoma model with Sox10 haploinsufficiency

    PMID:23913827

    Open questions at the time
    • Whether SOX10 regulates p21/p27 directly or solely through MITF was not determined
    • Contribution of non-MITF SOX10 targets to melanoma proliferation was unclear
  11. 2014 High

    SOX10 was found to directly activate MIA transcription and S100B expression, placing SOX10 upstream of melanoma invasion (via MIA) and Schwann cell myelination control (via S100B).

    Evidence ChIP and EMSA for SOX10 at MIA promoter, invasion rescue with MIA re-expression; SOX10-response-element mutagenesis in S100B promoter, shRNA knockdown, DRG myelination co-culture

    PMID:24608986 PMID:25536222

    Open questions at the time
    • Whether SOX10→MIA axis operates in non-melanoma neural crest tumors was untested
    • Upstream signals regulating SOX10 occupancy at the S100B locus were unknown
  12. 2015 High

    A reciprocal SOX9–SOX10 feedback loop was identified in melanoma: SOX9 is upregulated upon SOX10 loss and binds the SOX10 promoter to repress it, mediating anti-tumorigenic effects; simultaneously, Sox10 was shown to genetically interact with β1-integrin to control enteric NCC migration.

    Evidence SOX10 KD with SOX9 epistasis and ChIP for SOX9 at SOX10 promoter; Sox10/Itgb1 double-mutant mice with live-cell migration imaging

    PMID:23608456 PMID:25629959

    Open questions at the time
    • Whether the SOX9–SOX10 switch operates in normal melanocyte homeostasis was unclear
    • Direct versus indirect regulation of β1-integrin by SOX10 was not resolved
  13. 2016 High

    Genome-wide studies revealed that Chd7 physically interacts with Sox10 and co-occupies enhancers of myelinogenic genes, and that SOX10 directly activates MCM5 to promote melanocyte proliferation, expanding the known SOX10 target repertoire.

    Evidence ChIP-seq and co-IP for Chd7–Sox10, conditional Chd7 KO; ChIP for SOX10 at MCM5 promoter with rescue experiment

    PMID:26928066 PMID:27955842

    Open questions at the time
    • Whether Chd7 recruitment depends on Sox10 dimerization was not tested
    • Genome-wide SOX10 target overlap between melanocytes and oligodendrocytes was not compared
  14. 2017 High

    SOX10 was shown to recruit the BRG1 (SMARCA4) chromatin remodeler to melanocyte gene enhancers, and to transcriptionally induce miR-335/miR-338 that post-transcriptionally suppress Sox9, establishing chromatin remodeling and miRNA-mediated mechanisms through which SOX10 shapes differentiation.

    Evidence Co-IP of BRG1–SOX10, ChIP at Tyrp1 enhancer, conditional Smarca4 deletion; Sox10 ChIP at miR335/338 loci, luciferase assays with Sox9 3′-UTR

    PMID:28370559 PMID:28431046

    Open questions at the time
    • Whether BRG1 recruitment is required at all SOX10-dependent enhancers or a subset was unclear
    • Relative contribution of miR-mediated Sox9 repression versus direct transcriptional mechanisms in oligodendrocytes was not quantified
  15. 2018 High

    Post-translational regulation of SOX10 was defined: ERK phosphorylation antagonizes sumoylation at K55 to inhibit transcriptional activity, and SOX10 directly activates FOXD3 upon RAF inhibition, explaining adaptive resistance mechanisms in BRAF-mutant melanoma.

    Evidence Mass spectrometry, in vitro kinase assay, mutagenesis of phospho/sumo sites, ChIP at FOXD3 promoter, in vivo xenograft with SOX10 depletion

    PMID:29295999 PMID:29315345

    Open questions at the time
    • Which phosphatase(s) reverse ERK-mediated SOX10 phosphorylation was unknown
    • Whether all eight phosphorylation sites are functionally relevant in vivo was not established
  16. 2020 High

    Myrf was found to cooperate with Sox10 at myelination gene enhancers while simultaneously sequestering Sox10 away from precursor-phase genes, revealing a cofactor-mediated switch that redirects Sox10 activity during oligodendrocyte maturation.

    Evidence ChIP-seq for Sox10 and Myrf, co-IP, reporter assays with binding-site mutagenesis

    PMID:31828317

    Open questions at the time
    • Whether Myrf-mediated Sox10 sequestration involves liquid–liquid phase separation or stoichiometric titration was not resolved
    • Dynamics of Sox10 redistribution during the precursor-to-myelin transition were not captured in real time
  17. 2023 High

    In-frame SOX10 insertion/deletion mutations found in schwannomas retain DNA binding but lose transactivation, defining a hypomorphic mechanism that blocks Schwann cell differentiation and drives tumorigenesis.

    Evidence Comprehensive genomic profiling, EMSA, ChIP-seq, luciferase assays with mutant SOX10 in fetal glial cells

    PMID:37436963

    Open questions at the time
    • Whether these hypomorphic SOX10 mutants exert dominant-negative effects on wild-type SOX10 was not fully tested
    • The landscape of SOX10 mutations across all schwannoma subtypes is incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • Unresolved: how SOX10 selects between monomeric and dimeric binding modes at specific genomic loci in vivo, what determines lineage-specific cofactor choice, and whether SOX10's reported mitochondrial association has a physiological function remain open questions.
  • No genome-wide resolution of monomeric versus dimeric SOX10 occupancy in any cell type
  • Structural basis of SOX10 interaction with most cofactors (PAX3, Egr2, Myrf, BRG1) is unknown
  • Mitochondrial association of SOX10 (PMID 19304657) has not been independently replicated or given a clear function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 6 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 2
Partners
CHD7EGR2MYRFOLIG1PAX3SMARCA4SOX8SOX9

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 SOX10 is required for differentiation of peripheral glial cells (Schwann cells and satellite cells) from neural crest cells; Sox10 controls expression of ErbB3 (a Neuregulin receptor) in neural crest cells, and haploinsufficiency causes pigmentation and megacolon defects. Targeted Sox10 knockout mice and spontaneous Sox10 mutant (Dom) mice analyzed for neural crest derivative formation; ErbB3 expression assayed in mutants Genes & development High 11156606
1998 Premature termination of SOX10 (an HMG-box transcription factor) is responsible for loss of neural crest derivatives in Dom mice; Sox10 is essential for peripheral nervous system development and its dysfunction disrupts EDNRB expression in enteric ganglia precursors. Positional cloning, sequencing of Dom locus, in situ hybridization for Sox10 and Ednrb expression, apoptosis assays in mutant embryos Nature genetics High 9425902
1998 Sox10 frameshift mutation in Dom mouse causes functional inactivation; the C-terminus of SOX10 carries a transactivation domain, and all Waardenburg-Hirschsprung patient-derived mutant Sox10 proteins lack transactivation activity; synergistic enhancement of co-factor activity requires both DNA binding capacity and an N-terminal region of Sox10. In vitro transcription assays with mutant and wild-type Sox10 constructs; analysis of four patient-derived mutations in rat and human cDNA context The Journal of biological chemistry High 9722528
1998 Sox10 (Dominant megacolon locus) mutation causes functional inactivation of the encoded truncated protein; Sox10 is identified as a transcriptional regulator essential for mouse neural crest development. Chromosomal co-localization, Sox10 frameshift sequencing, Sox10 expression analysis in Dom gut and ganglia, functional inactivation assay of truncated protein Proceedings of the National Academy of Sciences of the United States of America High 9560246
2000 SOX10 directly binds and activates transcription from the MITF promoter; a WS4-linked mutant SOX10 acts as a dominant-negative repressor of MITF expression and reduces endogenous MITF protein levels; SOX10 and PAX3 interact directly by binding to a proximal MITF promoter region containing binding sites for both factors, synergistically activating MITF expression. Transfection/reporter assays, MITF promoter binding experiments, co-transfection with PAX3 and SOX10, Western blot for endogenous MITF, in situ hybridization in Dom mice Human molecular genetics / The Journal of biological chemistry High 10942418 10973953
2000 SOX10 functions through two distinct DNA-binding modes: monomeric binding and cooperative dimeric binding. Dimeric binding requires two heptameric Sox binding sites in specific orientation/spacing and is mediated by an N-terminal region conserved in Sox9; dimeric binding dramatically reduces the protein's off-rate and increases DNA bending angle. Electrophoretic mobility shift assay (EMSA), footprinting, mutagenesis of N-terminal dimerization region, DNA bending analysis Nucleic acids research High 10931919
2002 Specific amino acid residues in the conserved region immediately preceding the HMG domain of SOX10 are required for cooperative (dimeric) DNA binding; these residues cooperate with the first two alpha-helices of the HMG domain; cooperative binding is essential for full activation of the myelin protein zero (P0) promoter target gene. Site-directed mutagenesis, EMSA, transcriptional reporter assays Nucleic acids research High 12490719
2003 SOX10 preserves multipotency of neural crest stem cells by maintaining both glial and neuronal potential; SOX10 is required in vivo for induction of neurogenic transcription factors MASH1 and PHOX2B; simultaneously, SOX10 inhibits overt neuronal differentiation, and this activity requires higher Sox10 dosage than maintenance of neurogenic potential. In vitro neural crest stem cell (NCSC) culture, retroviral overexpression, loss-of-function analysis in Sox10 mutant embryos, lineage potential assays Neuron High 12691661
2004 Sox10 is required for terminal differentiation of oligodendrocytes in the CNS; Sox8 and Sox10 show functional redundancy in oligodendrocyte terminal differentiation: Sox8 can bind Sox10 response elements, form DNA-dependent heterodimers with Sox10, and activate Sox10-specific oligodendrocytic target genes. Sox8-deficient mouse analysis, Sox8/Sox10 double mutant analysis, EMSA for Sox8 binding to Sox10 response elements, heterodimerization assays, gene expression analysis Development (Cambridge, England) High 15102707
2007 Sox10 dimerization domain is required for immature Schwann cells to enter the promyelinating stage; a novel central transactivation domain is required for satellite glia differentiation and Schwann cell myelination, but not for early neural crest development or oligodendrocyte differentiation. Hypomorphic Sox10 mouse alleles with triple alanine substitution in dimerization domain and deletion of novel transactivation domain; phenotypic analysis of glial lineages Development (Cambridge, England) High 17699610
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; Olig2 does not bind Sox10 in zebrafish, but both OLIG1 and OLIG2 bind SOX10 in mouse. Co-immunoprecipitation of Olig1 and Sox10, luciferase reporter assays with mbp promoter, mutational analysis of binding sites The Journal of neuroscience High 18160645
2007 Sox10 interacts with Egr2/Krox20 to synergistically activate the myelin protein zero (Mpz) gene; activation of the Mpz intron element by Egr2 requires both Sox10-binding sites; Egr1 and Egr3 also cooperate with Sox10 at this element; composite Egr2/Sox10-binding site modules are conserved in other peripheral myelin genes (MAG, MBP, periaxin). Reporter assays, mutagenesis of Sox10 binding sites, co-transfection with Egr family members, chromatin immunoprecipitation, computational identification of regulatory modules Neuron glia biology High 18634568
2009 ARMCX3 (an armadillo repeat-containing protein of the mitochondrial outer membrane) physically interacts with SOX10; SOX10 is peripherally associated with the mitochondrial outer membrane in the cytoplasm; ARMCX3 overexpression increases mitochondrially associated SOX10 and enhances SOX10-dependent transactivation of nicotinic acetylcholine receptor alpha3 and beta4 subunit gene promoters. Co-immunoprecipitation, subcellular fractionation, mitochondrial membrane association assays, overexpression and transcriptional reporter assays The Journal of biological chemistry Medium 19304657
2011 Dimeric Sox10 binding to an inverted pair of Sox protein binding sites within core element 1 of the Oct6 Schwann cell enhancer (SCE) is essential for enhancer activity in vivo; monomeric Sox10 binding to this element is nonfunctional; Sox10-dependent Oct6 activation feeds forward to activate Krox20, timing and amplifying onset of peripheral myelination. Transgenic mouse in vivo enhancer assays, mutagenesis of Sox binding sites, phylogenetic conservation analysis The Journal of neuroscience High 21653862
2012 Sox10 activates Desert hedgehog (Dhh) expression in Schwann cells via direct monomeric binding to multiple sites in an intronic enhancer; this Sox10→Dhh axis promotes perineurial sheath formation, representing a non-cell-autonomous function of Sox10 in peripheral nerve development. Sox10 conditional deletion in Schwann cells, luciferase reporter assays with Dhh intronic enhancer, mutagenesis of Sox10 binding sites, in vivo transgenic mouse enhancer assays The Journal of neuroscience High 22514309
2012 Sox10 haploinsufficiency counteracts Nras(Q61K)-driven congenital naevus and melanoma formation; SOX10 silencing in human melanoma cells suppresses neural crest stem cell properties, counteracts proliferation and cell survival, and abolishes in vivo tumour formation. Genetic mouse melanoma model (Nras(Q61K) with Sox10 haploinsufficiency), SOX10 siRNA knockdown in human melanoma cells, in vivo xenograft assays Nature cell biology High 22772081
2013 Stable SOX10 knockdown in human melanoma cells arrests cell growth in G1, alters cellular morphology, and induces senescence; this is associated with reduced MITF expression, elevated p21WAF1 and p27KIP2, hypophosphorylated RB, and reduced E2F1 levels; Sox10 haploinsufficiency reduces melanoma initiation in Grm1(Tg) mouse model. Stable shRNA knockdown of SOX10 in melanoma cell lines, cell cycle analysis, Western blotting for cell cycle regulators, transgenic melanoma mouse model Cancer research High 23913827
2014 SOX10 directly binds the MIA (melanoma inhibitory activity) promoter and activates its transcription; SOX10 inhibition reduces MIA expression and melanoma cell invasion capacity; ectopic MIA expression rescues invasion defect caused by SOX10 inhibition, placing SOX10 upstream of MIA in a melanoma invasion pathway. RNA interference, invasion assays, EMSA, chromatin immunoprecipitation (ChIP), promoter-reporter assays, MIA re-expression rescue experiments The Journal of investigative dermatology High 24608986
2014 SOX10 transactivates the S100B promoter in Schwann cells via three core response elements (two in the promoter and one in intron 1); SOX10 or S100B knockdown enhances Schwann cell proliferation; S100B knockdown impairs myelination in dorsal root ganglia co-cultures. Promoter-reporter luciferase assays with mutagenesis of SOX10 response elements, shRNA knockdown of SOX10 and S100B, proliferation assays, DRG myelination co-culture assay PloS one High 25536222
2015 SOX9 is upregulated upon loss of SOX10 in melanoma and mediates the anti-tumorigenic effect; SOX9 binds the SOX10 promoter and induces downregulation of SOX10 expression, creating a feedback loop; SOX9 overexpression causes cell cycle arrest and apoptosis phenocopying low-SOX10 state; SOX9 is required in vitro and in vivo for anti-tumorigenic effects of SOX10 loss. SOX10 knockdown/knockout in melanoma cells and mouse model, SOX9 overexpression, ChIP for SOX9 binding to SOX10 promoter, epistasis analysis, in vivo tumor assays PLoS genetics High 25629959
2015 SOX10 modulates β1-integrin expression; genetic interaction between Sox10 and Itgb1 is required for normal enteric neural crest cell migration speed and directionality during ENS development. Double mutant mouse analysis (Sox10(lacZ/+); Ht-PA::Cre; beta1 conditional mutants), video-microscopy of enteric NCC migration, Sox10 overexpression and knockdown with β1-integrin expression analysis Developmental biology Medium 23608456
2016 Chd7 physically 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 chromatin occupancy (ChIP-seq), transcriptome profiling, co-immunoprecipitation of Chd7 and Sox10, conditional mouse knockout of Chd7 Nature neuroscience High 26928066
2016 SOX10 directly activates MCM5 (DNA replication licensing factor) transcription by binding conserved SOX10 consensus sequences in the MCM5 promoter; SOX10 reduction decreases melanocyte proliferation, partially rescued by MCM5 overexpression. SOX10 RNAi in melanocytes, ChIP for SOX10 binding at MCM5 promoter, promoter-reporter assay, MCM5 rescue experiment, Sox10/+ mouse melanoblast analysis Journal of dermatological science Medium 27955842
2017 BRG1 (SMARCA4, SWI/SNF chromatin remodeling complex subunit) physically interacts with SOX10 in differentiating melanocytes; SOX10 binds Tyrp1 distal enhancer and temporally recruits BRG1; BRG1 is required for chromatin remodeling at distal and proximal regulatory sites of melanocyte genes regulated by SOX10 and MITF (Dct, Tyrp1, Tyr). Sensitized mutagenesis screen, conditional Smarca4 deletion, co-immunoprecipitation of BRG1 and SOX10, ChIP for SOX10 and BRG1 at Tyrp1 enhancer, chromatin accessibility assays Nucleic acids research High 28431046
2017 Sox10 transcriptionally upregulates microRNAs miR335 and miR338 as direct targets; these microRNAs recognize the 3'-UTR of Sox9 mRNA and reduce Sox9 protein levels posttranscriptionally, enabling Sox10 to inversely couple Sox9 levels during oligodendrocyte differentiation. Sox10 deletion in oligodendroglial cells, miRNA expression analysis, luciferase assays with Sox9 3'-UTR, Sox10 ChIP at miR335/338 loci, mathematical modeling Glia High 28370559
2018 ERK phosphorylates SOX10 and inhibits its transcriptional activity by interfering with sumoylation of SOX10 at K55; sumoylation at K55 is essential for SOX10 transcriptional activity; SOX10 is necessary and sufficient for RAF inhibitor-induced FOXD3 expression by binding a regulatory element in the FOXD3 promoter; depletion of SOX10 sensitizes mutant BRAF melanoma cells to RAF inhibitors. Mass spectrometry for phosphorylation sites, site-directed mutagenesis of phospho and sumo sites, ChIP for SOX10 at FOXD3 promoter, in vitro kinase assay, in vivo xenograft with SOX10 depletion Nature communications High 29295999
2018 SOX10 is phosphorylated at eight sites; phosphorylation at S24, S45 and T240 (within MAPK/CDK binding motifs) affects SOX10 transcriptional activation, subcellular localization, and protein stability in melanoma cells. Mass spectrometry identification of phosphorylation sites, mutagenesis of phosphorylation sites, transcriptional reporter assays, subcellular localization imaging, protein stability assays PloS one Medium 29315345
2020 Myrf cooperates with Sox10 during induction of myelination genes by joint binding to the same regulatory regions; Myrf also inhibits Sox10 activity on genes essential during earlier oligodendroglial development via physical interaction and sequestration of Sox10 (on genes lacking Myrf binding sites), thereby redirecting Sox10 from precursor-phase genes to differentiation-phase genes. ChIP-seq for Sox10 and Myrf binding, co-immunoprecipitation of Myrf and Sox10, transcriptional reporter assays, mutagenesis of DNA-binding sites, gene expression analysis in oligodendrocytes Nucleic acids research High 31828317
2021 Akt phosphorylates FoxO1, preventing its nuclear translocation and repression of the Sox10 promoter; deletion of all three Akt isoforms in oligodendrocyte lineage cells causes loss of mature oligodendrocytes and downregulation of Sox10; FoxO1 with Akt phosphorylation site mutations represses Sox10 promoter activity and is enriched at the Sox10 promoter. Oligodendrocyte-specific Akt1/2/3 triple conditional knockout mice, Sox10 promoter reporter assays, ChIP for mutant FoxO1 at Sox10 promoter, Western blotting The Journal of neuroscience Medium 34385359
2023 Novel 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 a unique schwannoma subtype by impeding Schwann cell differentiation. Comprehensive genomic profiling, RNA sequencing, ChIP-seq, EMSA, luciferase reporter assays with wild-type and mutant SOX10 isoforms in fetal glial cells Neuro-oncology High 37436963
2001 colourless/sox10 in zebrafish is required for specification of non-ectomesenchymal neural crest derivatives; loss of sox10 causes failure of non-ectomesenchymal neural crest cells to migrate and differentiate, followed by apoptosis; sox10 controls nacre/mitf expression in melanophores; the phenotype is rescued by ectopic sox10 expression. Zebrafish sox10 mutant analysis, iontophoretic single-cell labeling, rescue by ectopic sox10 injection, in situ hybridization for mitf Development (Cambridge, England) High 11684650

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The transcription factor Sox10 is a key regulator of peripheral glial development. Genes & development 747 11156606
1998 Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nature genetics 624 9425902
2003 SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron 458 12691661
2001 Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates. Development (Cambridge, England) 432 11684650
2000 Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Human molecular genetics 370 10942418
1998 Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease. Proceedings of the National Academy of Sciences of the United States of America 301 9560246
2008 Sox10: a pan-schwannian and melanocytic marker. The American journal of surgical pathology 287 18636017
2012 Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma. Nature cell biology 218 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 194 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
2004 Transcription factors Sox8 and Sox10 perform non-equivalent roles during oligodendrocyte development despite functional redundancy. Development (Cambridge, England) 175 15102707
2016 Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination. Nature neuroscience 147 26928066
2000 The glial transcription factor Sox10 binds to DNA both as monomer and dimer with different functional consequences. Nucleic acids research 146 10931919
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
2005 Delayed Sry and Sox9 expression in developing mouse gonads underlies B6-Y(DOM) sex reversal. Developmental biology 125 15680364
1999 The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4) syndrome. Genome research 123 10077527
1998 Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients. The Journal of biological chemistry 117 9722528
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 98 26365194
1998 Expression of the SOX10 gene during human development. FEBS letters 95 9720918
2004 Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease. Human molecular genetics 93 15294878
2013 The role of SOX10 during enteric nervous system development. Developmental biology 84 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
2015 Antagonistic cross-regulation between Sox9 and Sox10 controls an anti-tumorigenic program in melanoma. PLoS genetics 81 25629959
2020 Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype. Nature communications 78 33339831
2013 SOX10 ablation arrests cell cycle, induces senescence, and suppresses melanomagenesis. Cancer research 78 23913827
2014 SOX10 promotes melanoma cell invasion by regulating melanoma inhibitory activity. The Journal of investigative dermatology 73 24608986
2014 FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands. Development (Cambridge, England) 71 24924191
2021 Using the lineage determinants Olig2 and Sox10 to explore transcriptional regulation of oligodendrocyte development. Developmental neurobiology 70 34480425
2022 Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma. Nature communications 69 35296667
2018 Disparate effects of DOM extracted from coastal seawaters and freshwaters on photodegradation of 2,4-Dihydroxybenzophenone. Water research 69 30616040
2013 Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas. British journal of cancer 67 23799842
2011 Functional dissection of the Oct6 Schwann cell enhancer reveals an essential role for dimeric Sox10 binding. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 21653862
2022 TRPS1, GATA3, and SOX10 expression in triple-negative breast carcinoma. Human pathology 65 35413381
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
2018 ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma. Nature communications 63 29295999
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
2017 BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation. Nucleic acids research 51 28431046
2000 Expression of the Sox10 gene during mouse inner ear development. Brain research. Molecular brain research 51 11113541
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 45 31828317
2018 Distinct interactions of Sox5 and Sox10 in fate specification of pigment cells in medaka and zebrafish. PLoS genetics 45 29621239
2014 SOX10 transactivates S100B to suppress Schwann cell proliferation and to promote myelination. PloS one 44 25536222
2006 Expression of SOX9 and SOX10 in central neuroepithelial tumor. Journal of neuro-oncology 44 16791471
2004 Sox10-rtTA mouse line for tetracycline-inducible expression of transgenes in neural crest cells and oligodendrocytes. Genesis (New York, N.Y. : 2000) 42 15493017
2008 SOX9 and SOX10 but not BRN2 are required for nestin expression in human melanoma cells. The Journal of investigative dermatology 40 18923447
2017 Utility of Sox10 labeling in metastatic breast carcinomas. Human pathology 38 28843711
2020 CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR-637 and up-regulating SOX10. Molecular oncology 37 33085838
2013 Value of SOX10 immunostaining in tumor diagnosis. Advances in anatomic pathology 35 23752089
2018 Identification and functional analysis of SOX10 phosphorylation sites in melanoma. PloS one 32 29315345
2015 Enteric neuron imbalance and proximal dysmotility in ganglionated intestine of the Sox10 Hirschsprung mouse model. Cellular and molecular gastroenterology and hepatology 32 25844395
2009 The armadillo repeat-containing protein, ARMCX3, physically and functionally interacts with the developmental regulatory factor Sox10. The Journal of biological chemistry 32 19304657
2017 SOX10 induced Nestin expression regulates cancer stem cell properties of TNBC cells. Biochemical and biophysical research communications 31 28189679
2020 A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein. Frontiers in molecular biosciences 30 33363209
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
2006 Paired overexpression of ErbB3 and Sox10 in pilocytic astrocytoma. Journal of neuropathology and experimental neurology 30 16896310
2018 SOX10 Immunoexpression in Basaloid Squamous Cell Carcinomas: A Diagnostic Pitfall for Ruling out Salivary Differentiation. Head and neck pathology 29 30498968
2023 Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs. Neuro-oncology 28 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 28 34385359
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
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 26 36343245
2019 Combined use of SOX10 and GATA3 in mammary carcinoma. Pathology, research and practice 26 31924335
2020 Immunohistological Expression of SOX-10 in Triple-Negative Breast Cancer: A Descriptive Analysis of 113 Samples. International journal of molecular sciences 25 32899175
2013 Sox10 and Itgb1 interaction in enteric neural crest cell migration. Developmental biology 25 23608456
2023 Clinical Significance of SOX10 Expression in Human Pathology. Current issues in molecular biology 22 38132479
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
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
2021 DNA-stable isotope probing (DNA-SIP) identifies marine sponge-associated bacteria actively utilizing dissolved organic matter (DOM). Environmental microbiology 20 34159693
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 Impact of manure-related DOM on sulfonamide transport in arable soils. Journal of contaminant hydrology 20 27450276
2014 Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10. American journal of medical genetics. Part A 20 24845202
2016 Sox10 regulates skin melanocyte proliferation by activating the DNA replication licensing factor MCM5. Journal of dermatological science 19 27955842
2012 Desert hedgehog links transcription factor Sox10 to perineurial development. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 22514309
2012 Expression of Sox10 and c-kit in sinonasal mucosal melanomas arising in the Chinese population. Head and neck pathology 17 22736149
2012 Interactions with DOM and biofilms affect the fate and bioavailability of insecticides to invertebrate grazers. Ecotoxicology (London, England) 17 22955550
2008 A Sox10 expression screen identifies an amino acid essential for Erbb3 function. PLoS genetics 17 18773073
2024 Spatial gradients and molecular transformations of DOM, DON and DOS in human-impacted estuarine sediments. Environment international 16 38430584
2023 SOX10. Journal of clinical pathology 16 37336549
2021 Functional in vivo characterization of sox10 enhancers in neural crest and melanoma development. Communications biology 16 34099848
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 The transcription factors Ets1 and Sox10 interact during murine melanocyte development. Developmental biology 16 25912689
2020 Oxaliplatin-induced neuropathic pain involves HOXA6 via a TET1-dependent demethylation of the SOX10 promoter. International journal of cancer 15 32428246
2020 Conjunctival nevi and melanoma: multiparametric immunohistochemical analysis, including p16, SOX10, HMB45, and Ki-67. Human pathology 15 32707054
2023 Targeting Upregulated cIAP2 in SOX10-Deficient Drug Tolerant Melanoma. Molecular cancer therapeutics 14 37343247
2021 SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma. Life (Basel, Switzerland) 14 33801642