Affinage

SOX8

Transcription factor SOX-8 · UniProt P57073

Length
446 aa
Mass
47.3 kDa
Annotated
2026-06-10
91 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX8 is a SOXE-group HMG-box transcription factor that binds canonical SOX DNA elements and activates transcription through a bipartite mechanism, in which a central transactivation domain (TAM) bearing a conserved EΦ[D/E]QYΦ motif and amphipathic α-helices synergizes with a C-terminal domain (TAC) (PMID:10684944, PMID:31194875). Across diverse developmental settings it acts largely redundantly with the related SOXE factors SOX9 and SOX10, typically as a weaker partner, and can form DNA-dependent heterodimers with SOX10 on shared response elements (PMID:15102707, PMID:15893981, PMID:16790476). In the testis, SOX8 reinforces SOX9 to establish and maintain Sertoli cell identity: combined loss produces defects more severe than SOX9 loss alone, the two factors sustain Dmrt1 and basal lamina integrity, and their joint ablation drives Sertoli-to-granulosa transdifferentiation and testis-to-ovary reprogramming (PMID:15056615, PMID:27328324, PMID:22837482, PMID:32450947). SOX8 maintains adult spermatogenesis and blood-testis barrier integrity through direct activation of the claudin-3 promoter (PMID:18342849, PMID:23595903). In the CNS, SOX8 promotes oligodendrocyte differentiation and remyelination redundantly with SOX10, regulating overlapping targets but with intrinsically lower transcriptional output that maps to the N-terminal third of the protein rather than the C-terminal transactivation domains (PMID:15893981, PMID:38097655, PMID:39201442, PMID:39769160). SOX8 also acts as a fate-determining factor at the top of the ear-determination network and specifies intestinal M cells by directly activating Gp2 downstream of RANKL-RelB signaling (PMID:30877171, PMID:35867760), and it directly regulates Wnt-pathway components during vertebrate gastrulation (PMID:41214364). It negatively regulates myoblast and osteoblast differentiation, in the latter case by suppressing Runx2 (PMID:15753123, PMID:12782625), while promoting growth-plate chondrocyte commitment together with SOX9 (PMID:38346197). SOX8 activity is post-translationally controlled by Aurora-A-mediated phosphorylation at Ser327 and by TRIM25-mediated ubiquitination and proteasomal degradation, and its transcription is set at the chromatin level by lncRNA Mrhl through CTCF/cohesin looping and PRC2 recruitment (PMID:32550913, PMID:35412350, PMID:40918640). In cancers, SOX8 acts as an oncogenic transcription factor that confers therapy resistance through direct activation of Wnt receptors and bypass-signaling genes (PMID:29071717, PMID:35195773, PMID:38046159).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2000 Medium

    Established that SOX8 is a functional sequence-specific transactivator and defined where in the protein its activation capacity resides, distinguishing it from SOX9/SOX10.

    Evidence In vitro transcription/reporter assays with domain mapping

    PMID:10684944

    Open questions at the time
    • No genomic target genes identified
    • Structural basis of the activation domains not resolved
  2. 2003 High

    Showed SOX8 engages a physiological target by binding the Amh promoter and synergizing with SF1, placing it in the Sertoli-cell sex-determination circuitry as a weaker SOX9-like activator.

    Evidence In vitro DNA binding, luciferase reporter, and co-IP for SOX8–SF1 interaction

    PMID:12732652

    Open questions at the time
    • In vitro only; in vivo relevance to Amh not tested
    • Relative contribution vs SOX9 not quantified
  3. 2003 Medium

    Revealed a non-developmental-glial role: SOX8 antagonizes myogenic differentiation by interfering with bHLH factors, showing it can act as a transcriptional repressor of lineage programs.

    Evidence Myoblast overexpression, myogenin promoter reporter, RT-PCR/Western

    PMID:12782625

    Open questions at the time
    • Direct DNA binding at myogenic loci not shown
    • Mechanism of bHLH interference unresolved
  4. 2004 High

    Defined functional redundancy with SOX9 in Sertoli cell differentiation, establishing the SOXE redundancy paradigm in the testis.

    Evidence Sox8/Sox9 double-knockout mouse epistasis

    PMID:15056615

    Open questions at the time
    • Direct shared target genes not defined here
    • Molecular basis of synergy not resolved
  5. 2004 High

    Demonstrated SOX8 forms DNA-dependent heterodimers with SOX10 and acts redundantly in oligodendrocyte differentiation, explaining its weaker contribution as a function of lower expression.

    Evidence EMSA, heterodimerization and reporter assays, Sox8-deficient mouse

    PMID:15102707

    Open questions at the time
    • Whether weakness is purely expression-level or intrinsic not settled here
    • Genome-wide co-occupancy not mapped
  6. 2005 High

    Extended the redundancy model across SOXE factors in oligodendrocyte development and to neural crest survival, showing SOX8 functions as a dose-sensitive modifier of SOX10.

    Evidence Sox8/Sox9 double-KO spinal cord and Sox8/Sox10 compound-mutant ENS genetics with apoptosis assays

    PMID:15572147 PMID:15893981

    Open questions at the time
    • Direct targets controlling progenitor survival not identified
    • Tissue-specific quantitative dose relationships not fully defined
  7. 2005 High

    Identified SOX8 as a negative regulator of osteoblast differentiation acting through Runx2 suppression, broadening its role to skeletal lineage restraint.

    Evidence Reciprocal Sox8 knockout and Col1a1-transgenic mouse models, bone histomorphometry, Runx2 qRT-PCR

    PMID:15753123

    Open questions at the time
    • Whether Runx2 regulation is direct not shown
    • Mechanism of repression undefined
  8. 2006 High

    Quantified the limits of SOXE interchangeability by replacing Sox10 with Sox8 in vivo, showing lineage-specific incomplete equivalence (e.g., failure to rescue melanocytes).

    Evidence Sox8-into-Sox10 knock-in mouse, multi-lineage histology

    PMID:16790476

    Open questions at the time
    • Molecular determinants of lineage-specific failure not mapped here
    • Distinct from later N-terminal domain mapping
  9. 2006 Medium

    Assigned SOX8 a role in neural crest induction timing and migration in a vertebrate embryo model.

    Evidence Morpholino knockdown in Xenopus, in situ hybridization, lineage tracing

    PMID:16943273

    Open questions at the time
    • Direct migration-controlling targets not identified
    • Morpholino specificity not independently confirmed
  10. 2008 High

    Established SOX8 as a critical regulator of adult Sertoli cell function and ongoing spermatogenesis, beyond embryonic differentiation.

    Evidence Sox8-null mouse histology and protein localization

    PMID:18342849

    Open questions at the time
    • Direct adult target genes not defined here
    • Age-dependence mechanism unresolved
  11. 2009 Medium

    Broadened SOX8 function to precursor maintenance in adipose tissue and to retinal Muller glia development under Notch control, indicating roles in progenitor pools across tissues.

    Evidence Sox8-KO mouse adipose analysis with in vitro rescue; retinal shRNA plus Notch/DAPT manipulation

    PMID:19286648 PMID:19490914

    Open questions at the time
    • Direct adipocyte/Muller-glia target genes not identified
    • Notch→Sox8 link is regulatory, not shown to be direct
  12. 2012 High

    Showed SOX9/SOX8 maintain testis cord basal lamina integrity through structural-gene programs, with loss triggering Sertoli transdifferentiation marked by FOXL2 upregulation.

    Evidence Conditional double-KO mouse, lineage tracing, marker immunostaining

    PMID:22837482

    Open questions at the time
    • Direct binding to collagen/scleraxis loci not demonstrated
    • Trigger of transdifferentiation not mechanistically resolved
  13. 2013 High

    Provided the first direct genomic target in the testis by demonstrating SOX8 binds and activates the claudin-3 promoter to maintain the blood-testis barrier.

    Evidence ChIP, Western, biotin tracer permeability assay, electron microscopy in Sox8-deficient mice

    PMID:23595903

    Open questions at the time
    • Other barrier targets not surveyed
    • Microtubule destabilization mechanism indirect
  14. 2016 High

    Placed SOX9/SOX8 above Dmrt1 in maintaining adult testicular identity, showing their combined loss reprograms the gonad toward the ovarian fate.

    Evidence Conditional Sox9 ablation on Sox8-null background, lineage-marker immunostaining

    PMID:27328324

    Open questions at the time
    • Direct vs indirect Dmrt1 regulation not resolved
    • SOX8-only contribution not isolated
  15. 2017 Medium

    Defined the chromatin-level control of Sox8 transcription by lncRNA Mrhl in spermatogonia and tied Sox8 output to Wnt signaling, and separately revealed an oncogenic Wnt-receptor target program.

    Evidence ChIP, RNA-protein interaction and reporter assays at the Sox8 promoter; ChIP/reporter for SOX8→FZD7 in tongue carcinoma

    PMID:28461394 PMID:29071717

    Open questions at the time
    • Mrhl mechanism not yet resolved to chromatin architecture (addressed later)
    • FZD7 study single-lab without in vivo validation
  16. 2018 Medium

    Identified cooperating partners and direct cis-elements: SOX8 cooperates with SF1/cJUN at the Gja1/Cx43 promoter in Sertoli cells and with Sall4 at the Sox3 otic enhancer in placode specification.

    Evidence Co-transfection/reporter assays at Gja1; ChIP-qPCR and reporter at the Sox3 Otic1 enhancer

    PMID:29520762 PMID:30080944

    Open questions at the time
    • In vivo requirement of these elements not tested
    • Single-lab reporter-based evidence
  17. 2019 High

    Established SOX8 as the direct transcriptional driver of intestinal M cell identity via the Gp2 promoter downstream of RANKL-RelB, and refined the SOXE bipartite transactivation model with a conserved TAM motif.

    Evidence Sox8-KO mouse with ChIP/reporter at Gp2 and immune readouts; mutagenesis/reporter mapping of TAM/TAC across SOXE proteins

    PMID:30877171 PMID:31194875

    Open questions at the time
    • Cofactors at the Gp2 promoter not fully defined
    • Structural model of TAM-TAC synergy not solved
  18. 2020 High

    Revealed post-translational and upstream control of SOX8: Aurora-A phosphorylates Ser327 to drive a senescence/glycolysis program and chemoresistance, and confirmed SF1 recruitment to the Cx43 promoter.

    Evidence IP/MS/FRET-FLIM, in vitro phosphorylation, ChIP/reporter in ovarian cancer; ChIP/reporter for SF1 at Cx43

    PMID:32550913 PMID:33088929

    Open questions at the time
    • Whether Ser327 phosphorylation operates in normal development not tested
    • Structural consequence of phosphorylation unknown
  19. 2020 High

    Demonstrated SOX8 alone can compensate for SOX9 loss in driving Sertoli differentiation, sharpening the functional-equivalence picture during sex reversal.

    Evidence Rspo1/Sox8/Sox9 compound-mutant mouse genetics with gonad marker analysis

    PMID:32450947

    Open questions at the time
    • Threshold of SOX8 sufficiency not quantified
    • Direct targets mediating compensation not identified
  20. 2021 Medium

    Connected SOX8 to upstream regulators and a cofactor in neural/Sertoli contexts: NFIA directly activates Sox8 and SOX8 partners with STAT3/p300 in astrocytic differentiation, while hnRNPU enhances Sox8/Sox9 expression in Sertoli cells.

    Evidence ChIP, co-IP, reporter and differentiation assays; Sertoli conditional hnRNPU-KO with ChIP/co-IP

    PMID:34677001 PMID:34815802

    Open questions at the time
    • Direct astrocytic SOX8 targets not mapped
    • hnRNPU effect on Sox8 vs Sox9 not separable
  21. 2022 Medium

    Resolved the chromatin architecture by which Mrhl gates Sox8 (CTCF/cohesin silencer loop and PRC2 recruitment versus YY1 enhancer loop), and expanded oncogenic SOX8 mechanisms to EZH2/SPARC and HGF/MET resistance pathways.

    Evidence 3C/loop assays, triplex assay, PRC2/YY1 ChIP at Sox8 locus; ChIP/reporter for SOX8→EZH2 and SOX8→HGF in cancer

    PMID:35173526 PMID:35195773 PMID:35412350

    Open questions at the time
    • Cancer mechanisms each single-lab
    • In vivo relevance of the Mrhl architecture beyond spermatogonia untested
  22. 2022 High

    Positioned SOX8 at the top of the ear-determination hierarchy, showing it is a fate-instructive master factor capable of converting cranial ectoderm to ear progenitors.

    Evidence Gain- and loss-of-function in cranial ectoderm with ATAC-seq/RNA-seq

    PMID:35867760

    Open questions at the time
    • Direct pioneer activity on chromatin not formally demonstrated
    • Downstream direct targets not individually validated
  23. 2023 Medium

    Defined SOX8 requirement for OPC proliferation and timely remyelination in a demyelination model, and added an oncogenic FZD6/Wnt target axis.

    Evidence Sox8-KO cuprizone model with myelin marker IHC; reporter/knockdown-rescue for SOX8→FZD6 in colorectal carcinoma

    PMID:38046159 PMID:38097655

    Open questions at the time
    • Direct OPC-proliferation targets not identified
    • FZD6 study lacks direct ChIP/in vivo confirmation
  24. 2024 Medium

    Showed SOX8/SOX9 jointly drive growth-plate chondrocyte commitment and that SOX8's intrinsically distinct (and in oligodendrocytes weaker) transcriptional activity maps to its N-terminal third, not the C-terminal transactivation domains.

    Evidence Compound conditional KO and reciprocal overexpression in chondrocytes; adult Sox8/Sox10 KO RNA-seq and domain-swap experiments in oligodendroglial cells

    PMID:38346197 PMID:39201442 PMID:39769160

    Open questions at the time
    • Molecular basis of N-terminal activity difference not resolved
    • Whether protein-stability difference fully explains chondrocyte potency untested
  25. 2025 Medium

    Established TRIM25 as an E3 ligase degrading SOX8, identified OSR2 and integrin programs as downstream effectors, and showed SOX8 directly regulates kremen2 to modulate Wnt during gastrulation.

    Evidence Co-IP/ubiquitination/reporter (TRIM25, OSR2) in ligament fibroblasts; ChIP/RNA-seq (EHMT1→BRD4→SOX8→integrin) in rhabdomyosarcoma; CRISPR/ChIP/transcriptomics for Sox8→kremen2 in Xenopus

    PMID:40467997 PMID:40918640 PMID:41214364

    Open questions at the time
    • TRIM25 and EHMT1 axes each single-lab
    • Integration of degradation control with developmental SOX8 dosage untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SOX8's intrinsic transcriptional weakness, partner selectivity, and post-translational regulation are integrated to determine context-specific outputs across redundancy with SOX9/SOX10.
  • No structure of the TAM/TAC transactivation surface or N-terminal activity-modulating region
  • Genome-wide SOX8 vs SOX9/SOX10 occupancy maps across tissues incomplete
  • Whether Aurora-A/TRIM25 regulation operates in developmental contexts unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-1474165 Reproduction 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 3
Partners
AURORA-AEP300HNRNPUSF1SOX10SOX9STAT3TRIM25

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 SOX8 binds specifically to SOX binding sites within the Amh minimal promoter and activates Amh transcription synergistically with SF1 through direct protein-protein interaction, albeit at lower levels than SOX9. In vitro DNA binding assays, luciferase reporter assays, co-immunoprecipitation/protein-protein interaction assays The Journal of biological chemistry High 12732652
2000 SOX8 protein binds to canonical SOX target DNA sequences and activates transcription through two separate trans-activation regions located in the central part of the protein (distinct from the C-terminal location in SOX9/SOX10). In vitro transcription/reporter assays, protein domain mapping Nucleic acids research Medium 10684944
2004 Double knockout analyses in mice show that Sox8 reinforces Sox9 function in testis differentiation; combined loss of Sox8 and Sox9 causes more severe defects than loss of Sox9 alone, establishing genetic redundancy between the two factors in Sertoli cell differentiation. Conditional gene targeting / double knockout mouse genetics, epistasis analysis Development (Cambridge, England) High 15056615
2004 Sox8 binds to naturally occurring Sox10 response elements and forms DNA-dependent heterodimers with Sox10, activating Sox10-specific oligodendrocytic target genes; Sox8 and Sox10 act redundantly in terminal oligodendrocyte differentiation, with Sox8 having weaker impact due to lower expression levels. Electrophoretic mobility shift assay / DNA binding, heterodimer formation assay, reporter gene assays, Sox8-deficient mouse analysis Development (Cambridge, England) High 15102707
2005 Sox8 acts as a modifier gene for Sox10-dependent enteric nervous system development; loss of Sox8 alleles in Sox10 heterozygous mice dramatically increases apoptosis in vagal neural crest cells, reducing the pool of undifferentiated progenitors required for gut colonization. Genetic epistasis (Sox8/Sox10 compound mutant mice), apoptosis assays, lineage analysis Developmental biology High 15572147
2005 Combined loss of Sox8 and Sox9 in the embryonic spinal cord leads to near-complete loss of oligodendrocytes, while loss of Sox8 alone only enhances the Sox9-dependent defect, establishing that oligodendrocyte development relies on differential contribution of all three group E Sox proteins. Double knockout mouse genetics, cell counting, proliferation and apoptosis assays Developmental biology High 15893981
2005 Sox8 negatively regulates osteoblast differentiation; Sox8-deficient mice show precocious osteoblast differentiation and low bone mass, and Sox8 overexpression under Col1a1 promoter strongly reduces Runx2 expression and impairs bone formation. Sox8 knockout and transgenic mouse models, bone histomorphometry, ex vivo osteoblast differentiation, qRT-PCR for Runx2 The Journal of cell biology High 15753123
2003 Sox8 overexpression in myoblasts inhibits myotube formation, reduces MyoD and myogenin expression, and strongly reduces basal and MyoD-induced myogenin promoter activity, acting as a negative regulator of skeletal muscle differentiation by interfering with myogenic bHLH proteins. Overexpression in myoblast cell culture, luciferase reporter assay, Western blot/RT-PCR The Journal of biological chemistry Medium 12782625
2006 In Xenopus, morpholino-mediated knockdown of Sox8 delays the timing of neural crest induction at the neural plate border and prevents neural crest cell migration into the periphery, without affecting specification or survival of progenitors. Morpholino knockdown in Xenopus embryos, in situ hybridization, lineage tracing Development (Cambridge, England) Medium 16943273
2006 Replacement of Sox10 with Sox8 by targeted mutagenesis in mice shows incomplete functional equivalence: Sox8 almost fully rescues peripheral nervous system glia and neurons but fails to rescue melanocyte development, and only partially rescues enteric nervous system and oligodendrocyte defects. Targeted gene replacement (knock-in) mouse genetics, histological and molecular analysis of multiple lineages Development (Cambridge, England) High 16790476
2008 SOX8 protein is a product of adult Sertoli cells; its elimination causes age-dependent deregulation of spermatogenesis including spermatocyte/spermatid sloughing, spermiation failure, and progressive disorganization of the spermatogenic cycle, establishing SOX8 as a critical regulator of adult Sertoli cell function. Sox8 null mouse analysis, histological/cellular analysis, protein localization Developmental biology High 18342849
2009 Adult Sox8-deficient mice develop progressive degeneration of adipose tissue, with elevated preadipocyte marker Pref-1 and impaired differentiation of Sox8-deficient fibroblasts to adipocytes in culture, which is rescued by reintroducing Sox8, suggesting a precursor-intrinsic role in adipocyte pool replenishment. Sox8 knockout mouse analysis, cell culture differentiation assay, rescue experiment by Sox8 re-expression Journal of lipid research Medium 19286648
2013 SOX8 binds directly to the claudin-3 promoter (confirmed by ChIP) in Sertoli cells; Sox8-deficient mice have decreased claudin-3 protein, increased blood-testis barrier permeability (biotin tracer), and destabilized microtubule structures in testes. Chromatin immunoprecipitation, Western blot, biotin tracer permeability assay, electron microscopy Biology of reproduction High 23595903
2016 Ablation of Sox9 in Sertoli cells of adult Sox8-null mice causes testis-to-ovary genetic reprogramming, with Sertoli cells transdifferentiating into granulosa-like cells; SOX9/8 maintain Dmrt1 expression and are required for adult testis maintenance. Conditional knockout mouse genetics (Sox9 ablation on Sox8-/- background), histology, immunostaining for lineage markers eLife High 27328324
2020 Aurora-A kinase directly binds SOX8 and phosphorylates it at Ser327, which enhances FOXK1 expression and regulates downstream genes related to cell senescence (hTERT, P16) and glycolysis (LDHA, HK2), promoting cisplatin resistance in ovarian cancer. Immunoprecipitation, mass spectrometry, FRET-FLIM, luciferase reporter assay, ChIP, in vitro phosphorylation assay Theranostics High 32550913
2017 SOX8 binds to the promoter region of Frizzled-7 (FZD7) and induces FZD7-mediated activation of the Wnt/β-catenin pathway, conferring chemoresistance and cancer stem-like properties in cisplatin-resistant tongue squamous cell carcinoma. Chromatin immunoprecipitation, luciferase reporter assay, SOX8 knockdown with functional rescue by active β-catenin International journal of cancer Medium 29071717
2019 Sox8 expression in intestinal M cells requires RANKL-RelB signaling; Sox8 directly binds the Gp2 promoter (by ChIP and luciferase assay) to drive Gp2 expression; Sox8-deficient mice have markedly fewer mature M cells and reduced antigen uptake and IgA responses. Sox8 knockout mouse, chromatin immunoprecipitation, luciferase reporter assay, flow cytometry, immunostaining The Journal of experimental medicine High 30877171
2019 SOXE proteins (SOX8, SOX9, SOX10) share a bipartite transactivation mechanism: a transactivation domain in the middle of the protein (TAM) with amphipathic α-helices synergizes with a C-terminal domain (TAC); TAM contains a conserved EΦ[D/E]QYΦ motif required for function. Mutagenesis, transactivation reporter assays, structural prediction, evolutionary sequence analysis Nucleic acids research High 31194875
2018 SOX8 and SF1 cooperate to regulate Gja1/Cx43 expression in Sertoli cells; cJUN cooperates with SOX8 or SOX9 via the -47 bp AP-1 element of the Gja1 promoter to drive Cx43 expression. Co-transfection/luciferase reporter assays with Gja1 promoter constructs, in Sertoli cell lines Molecular reproduction and development Medium 30080944
2020 SOX8 and SF-1 cooperate to activate Cx43/connexin43 expression in Sertoli cells; SF-1 is recruited to the proximal -132 to -26 bp region of the Cx43 promoter as confirmed by ChIP. Co-transfection luciferase reporter assays, chromatin immunoprecipitation Biochemistry and biophysics reports Medium 33088929
2021 Sox8 is a direct transcriptional target of Nfia in neural stem/precursor cells; Sox8 promotes LIF-induced astrocytic differentiation by associating with STAT3 through transcriptional coactivator p300, without inducing DNA demethylation of Gfap. ChIP for Nfia binding at Sox8 locus, Sox8 knockdown/overexpression, co-immunoprecipitation of Sox8-p300-STAT3, reporter assay Pharmacology research & perspectives Medium 34677001
2009 Sox8 and Sox9 are required for Müller glial cell development in mouse retina; both genes are regulated by Notch signaling, which controls their transcription as shown using activated Notch and gamma-secretase inhibitor DAPT. shRNA knockdown, activated Notch overexpression, gamma-secretase inhibitor treatment, retinal cell proportion analysis Experimental eye research Medium 19490914
2012 Sox9 and Sox8 jointly maintain basal lamina integrity of testis cords by controlling expression of collagen IV, collagen IXa3, testatin, and Scleraxis; combined loss leads to delamination of Sertoli cells and progressive FOXL2 upregulation indicating transdifferentiation. Conditional double-knockout mouse genetics, lineage tracing, immunostaining for structural/molecular markers Biology of reproduction High 22837482
2020 Genetic ablation of Sox8 and Sox9 together, but not either alone, prevents ovarian-to-testicular reprogramming in XX Rspo1-null mice, demonstrating that Sox8 alone can compensate for Sox9 loss in driving Sertoli cell differentiation during female-to-male sex reversal. Triple mutant mouse genetics (Rspo1-/- Sox8-/- Sox9 compound mutants), gonad morphology and marker analysis eLife High 32450947
2017 In mouse spermatogonial cells, lncRNA Mrhl binds the Sox8 promoter along with Myc-Max-Mad transcription factors, corepressor Sin3a, and coactivator Pcaf to regulate Sox8 transcription; upon Wnt signaling activation and Mrhl downregulation, Sox8 directly regulates expression of premeiotic and meiotic markers. Chromatin immunoprecipitation, RNA-protein interaction assays, promoter reporter assays, Sox8 knockdown/overexpression Molecular and cellular biology Medium 28461394
2022 lncRNA Mrhl regulates Sox8 in spermatogonia via CTCF/cohesin-mediated chromatin looping that brings the Sox8 promoter in contact with a silencer element when Mrhl is present; Mrhl interacts with the Sox8 locus through DNA:DNA:RNA triplex formation recruiting PRC2; upon Mrhl downregulation, a promoter-enhancer loop mediated by YY1 activates Sox8 transcription. Chromatin conformation capture (3C/loop assays), triplex formation assay, PRC2 ChIP, YY1 ChIP Molecular and cellular biology Medium 35412350
2022 Sox8 is placed at the top of the ear determination network in cranial ectoderm; introducing Sox8 into non-ear cranial ectoderm converts cells to ear progenitors and activates programs for ear morphogenesis and neurogenesis, as established by gain-of-function and multiomics approaches. Loss-of-function experiments, Sox8 gain-of-function in cranial ectoderm, multiomics (ATAC-seq/RNA-seq) Proceedings of the National Academy of Sciences of the United States of America High 35867760
2024 SOX8 and SOX9 jointly promote commitment of growth plate reserve chondrocytes to columnar proliferating cells; compound Sox8/Sox9 inactivation in limb skeletal cells causes 15-20% shortening of long bones; SOX8 overexpression is more efficient than SOX9 at promoting chondrocyte proliferation and differentiation, possibly due to greater protein stability. Conditional single and compound knockout mouse genetics, SOX8/SOX9 overexpression in chondrocytes, growth plate histomorphometry, high-throughput gene expression assays Proceedings of the National Academy of Sciences of the United States of America High 38346197
2023 Sox8 is essential for oligodendrocyte precursor cell proliferation and timely remyelination; Sox8-/- mice in the cuprizone model show reduced OPC proliferation at peak demyelination and fewer mature oligodendrocytes during remyelination, with delayed myelin marker recovery. Sox8 knockout mouse in cuprizone demyelination model, immunohistochemistry for oligodendroglial/myelin markers, motor performance testing Scientific reports Medium 38097655
2022 SOX8 transcriptionally regulates EZH2 in pancreatic cancer, which then reduces SPARC expression via histone methylation, thereby reducing albumin-bound paclitaxel transport and conferring chemoresistance. ChIP, reporter assays, EZH2 inhibitor rescue, Western blot International journal of biological sciences Medium 35173526
2022 SOX8 binds directly to the HGF promoter and transcriptionally activates HGF expression, which activates the HGF/MET bypass pathway to induce cetuximab resistance in colorectal cancer cells. Chromatin immunoprecipitation, promoter-luciferase reporter assay Cancer chemotherapy and pharmacology Medium 35195773
2023 SOX8 directly binds the FZD6 promoter and transcriptionally activates FZD6-dependent Wnt/β-catenin signaling to promote tumor growth in colorectal carcinoma; SOX8 knockdown reduces phospho-GSK3β and FZD6, rescued by FZD6 restoration. Luciferase reporter assay, knockdown/rescue experiment, Western blot Heliyon Medium 38046159
2025 EHMT1 upregulates SOX8 expression via regulation of BRD4 expression, leading to increased BRD4 occupancy at the SOX8 promoter; SOX8 in turn regulates integrin gene expression to promote migration and invasion in embryonal rhabdomyosarcoma. ChIP for BRD4 at SOX8 promoter, EHMT1/SOX8 knockdown, RNA-seq, in vitro migration/invasion and in vivo metastasis assays British journal of cancer Medium 40467997
2025 TRIM25 is an E3 ubiquitin ligase that interacts with SOX8 (by co-immunoprecipitation) and promotes its ubiquitination and proteasomal degradation; reduced SOX8 levels promote osteogenic differentiation of ligament fibroblasts, and SOX8 inhibits this process partly by transcriptionally activating OSR2. Co-immunoprecipitation, ubiquitination assay, mass spectrometry, dual-luciferase reporter assay, in vitro and in vivo osteogenic differentiation models JOR spine Medium 40918640
2025 In Xenopus, Sox8 directly binds the kremen2 (Wnt inhibitor) promoter (confirmed by ChIP) and transcriptionally activates kremen2 expression; Sox8 depletion via CRISPR leads to blastopore closure defects, impaired AP axis elongation, abnormal ventral expansion of wnt11b, increased nuclear β-catenin, and reduced BMP signaling, establishing Sox8 as a regulator of Wnt signaling during gastrulation. CRISPR-DiCas7-11 depletion, ChIP, transcriptomic analysis, in situ hybridization, β-catenin localization EMBO reports High 41214364
2018 In the chicken otic placode, Sox8 binds the Otic1 enhancer of the Sox3 gene (confirmed by ChIP-qPCR) and cooperates with Sall4 to activate Sox3 transcription, establishing a direct transcriptional regulatory interaction in otic placode specification. ChIP-qPCR, luciferase reporter assays, enhancer dissection Development, growth & differentiation Medium 29520762
2024 In adult oligodendrocytes, Sox8 deletion alone does not alter oligodendrocyte numbers or myelin structure, but combined Sox8/Sox10 deletion causes substantially greater alterations in oligodendrocyte expression profiles than Sox10 deletion alone; the differential transcriptional activity of Sox8 vs Sox10 depends on the N-terminal one-third of the protein, not the known C-terminal transactivation domains. Targeted Sox8/Sox10 deletion in adult mouse brains, RNA-sequencing of corpus callosum, protein domain swap experiments in oligodendroglial cell line International journal of molecular sciences Medium 39201442
2024 Molecular analysis in the oligodendroglial Oln93 cell line shows that Sox8 regulates the same gene targets as Sox10 but with substantially lower transcriptional activity despite comparable binding to regulatory regions; the differential activity maps to the N-terminal one-third of the Sox protein, not the C-terminal transactivation domains. Gene replacement in oligodendroglial cell line, transcriptomic profiling (RNA-seq), chromatin binding comparison International journal of molecular sciences Medium 39769160
2021 hnRNPU interacts with SOX9 and enhances Sox8 and Sox9 expression in Sertoli cells by directly binding to their promoter regions; hnRNPU conditional knockout in Sertoli cells causes testicular atrophy, depletion of Sertoli and germ cells, and male sterility. Co-immunoprecipitation, ChIP-qPCR, luciferase assay, conditional knockout mouse, RNA-seq Theranostics Medium 34815802

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Functional analysis of Sox8 and Sox9 during sex determination in the mouse. Development (Cambridge, England) 450 15056615
2004 Transcription factors Sox8 and Sox10 perform non-equivalent roles during oligodendrocyte development despite functional redundancy. Development (Cambridge, England) 175 15102707
2005 Identification of Sox8 as a modifier gene in a mouse model of Hirschsprung disease reveals underlying molecular defect. Developmental biology 144 15572147
2001 Idiopathic weight reduction in mice deficient in the high-mobility-group transcription factor Sox8. Molecular and cellular biology 143 11564878
2020 Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Theranostics 132 32550913
2003 SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro. The Journal of biological chemistry 128 12732652
2009 SOX E genes: SOX9 and SOX8 in mammalian testis development. The international journal of biochemistry & cell biology 120 19647095
2017 SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β-catenin pathway. International journal of cancer 115 29071717
2008 Quantitative assessment of glial cells in the human and guinea pig enteric nervous system with an anti-Sox8/9/10 antibody. The Journal of comparative neurology 104 18512230
2008 Sox8 is a critical regulator of adult Sertoli cell function and male fertility. Developmental biology 89 18342849
2006 Functional analysis of Sox8 during neural crest development in Xenopus. Development (Cambridge, England) 89 16943273
2005 Impact of transcription factor Sox8 on oligodendrocyte specification in the mouse embryonic spinal cord. Developmental biology 86 15893981
2016 Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration. eLife 83 27328324
2003 Sox8 is a specific marker for muscle satellite cells and inhibits myogenesis. The Journal of biological chemistry 82 12782625
2006 Replacement of the Sox10 transcription factor by Sox8 reveals incomplete functional equivalence. Development (Cambridge, England) 81 16790476
2000 Cloning and characterisation of the Sry-related transcription factor gene Sox8. Nucleic acids research 76 10684944
2005 The high mobility group transcription factor Sox8 is a negative regulator of osteoblast differentiation. The Journal of cell biology 74 15753123
2009 The group E Sox genes Sox8 and Sox9 are regulated by Notch signaling and are required for Müller glial cell development in mouse retina. Experimental eye research 68 19490914
2019 Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice. The Journal of experimental medicine 52 30877171
2018 Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies. Human molecular genetics 51 29373757
2000 The SOX8 gene is located within 700 kb of the tip of chromosome 16p and is deleted in a patient with ATR-16 syndrome. Genomics 50 10662550
2019 The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite transactivation mechanism. Nucleic acids research 48 31194875
2002 Expression of Sox8, Sox9 and Sox10 in the developing valves and autonomic nerves of the embryonic heart. Mechanisms of development 46 12351187
2017 Mrhl Long Noncoding RNA Mediates Meiotic Commitment of Mouse Spermatogonial Cells by Regulating Sox8 Expression. Molecular and cellular biology 45 28461394
2000 SOX8 expression during chick embryogenesis. Mechanisms of development 39 10842083
2012 Sox9 and Sox8 are required for basal lamina integrity of testis cords and for suppression of FOXL2 during embryonic testis development in mice. Biology of reproduction 38 22837482
2021 hnRNPU in Sertoli cells cooperates with WT1 and is essential for testicular development by modulating transcriptional factors Sox8/9. Theranostics 35 34815802
2014 Oncogenicity of the transcription factor SOX8 in hepatocellular carcinoma. Medical oncology (Northwood, London, England) 34 24643625
2020 Low expression of CircRNA HIPK3 promotes osteoarthritis chondrocyte apoptosis by serving as a sponge of miR-124 to regulate SOX8. European review for medical and pharmacological sciences 29 32767319
2005 Expression of Sox8, Sf1, Gata4, Wt1, Dax1, and Fog2 in the mouse ovarian follicle: implications for the regulation of Amh expression. Molecular reproduction and development 29 15625693
2023 Excessive SOX8 reprograms energy and iron metabolism to prime hepatocellular carcinoma for ferroptosis. Redox biology 27 38142583
2013 SOX8 regulates permeability of the blood-testes barrier that affects adult male fertility in the mouse. Biology of reproduction 26 23595903
2021 SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia. Pharmacology research & perspectives 22 34677001
2020 Sox8 and Sox9 act redundantly for ovarian-to-testicular fate reprogramming in the absence of R-spondin1 in mouse sex reversals. eLife 22 32450947
2014 Brief report: importance of SOX8 for in vitro chondrogenic differentiation of human mesenchymal stromal cells. Stem cells (Dayton, Ohio) 20 24449344
2023 Downregulation of Sox8 mediates monosodium urate crystal-induced autophagic impairment of cartilage in gout arthritis. Cell death discovery 19 36918540
2017 Selective neuronal expression of the SoxE factor, Sox8, in direct pathway striatal projection neurons of the developing mouse brain. The Journal of comparative neurology 19 28472858
2004 Sox8 is expressed at similar levels in gonads of both sexes during the sex determining period in turtles. Developmental dynamics : an official publication of the American Association of Anatomists 19 15366016
2023 Promotive role of USP29-mediated deubiquitination in malignant proliferation of colorectal cancer cells via the KIAA1429/SOX8 axis. Biomolecules & biomedicine 18 36373629
2018 Gja1 expression is regulated by cooperation between SOX8/SOX9 and cJUN transcription factors in TM4 and 15P-1 Sertoli cell lines. Molecular reproduction and development 18 30080944
2014 miRNA-124 down-regulates SOX8 expression and suppresses cell proliferation in non-small cell lung cancer. International journal of clinical and experimental pathology 18 25550787
2021 Notoginsenoside R2 reduces Aβ25-35-induced neuronal apoptosis and inflammation via miR-27a/SOX8/β-catenin axis. Human & experimental toxicology 17 34533063
2012 Homologues of sox8 and sox10 in the orange-spotted grouper Epinephelus coioides: sequences, expression patterns, and their effects on cyp19a1a promoter activities in vitro. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 16 22580033
2024 Skeletal growth is enhanced by a shared role for SOX8 and SOX9 in promoting reserve chondrocyte commitment to columnar proliferation. Proceedings of the National Academy of Sciences of the United States of America 15 38346197
2009 Downstream genes of Sox8 that would affect adult male fertility. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 15 19339814
2020 Long Noncoding RNA Taurine-Upregulated Gene 1 Knockdown Protects Cardiomyocytes Against Hypoxia/Reoxygenation-induced Injury Through Regulating miR-532-5p/Sox8 Axis. Journal of cardiovascular pharmacology 14 32833900
2022 Two Different Copy Number Variations of the SOX5 and SOX8 Genes in Yak and Their Association with Growth Traits. Animals : an open access journal from MDPI 13 35739923
2014 miRNA-124 down-regulates SOX8 expression and suppresses cell proliferation in non-small cell lung cancer. International journal of clinical and experimental pathology 13 25400731
2022 Sox8 remodels the cranial ectoderm to generate the ear. Proceedings of the National Academy of Sciences of the United States of America 12 35867760
2020 MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8. Cancer management and research 12 33061629
2019 Transcriptomic analysis of overexpressed SOX4 and SOX8 in TM4 Sertoli cells with emphasis on cell-to-cell interactions. Biochemical and biophysical research communications 12 30922563
2010 A Case of Agonadism, Skeletal Malformations, Bicuspid Aortic Valve, and Delayed Development with a 16p13.3 Duplication Including GNG13 and SOX8 Upstream Enhancers: Are Either, Both or Neither Involved in the Phenotype? Molecular syndromology 12 21373258
2023 Endogenous Sox8 is a critical factor for timely remyelination and oligodendroglial cell repletion in the cuprizone model. Scientific reports 11 38097655
2022 SOX8 Affects Tumoral SPARC Expression by Regulating EZH2 to Attenuate Effectiveness of albumin-bound paclitaxel in PDAC. International journal of biological sciences 11 35173526
2009 Adult-onset degeneration of adipose tissue in mice deficient for the Sox8 transcription factor. Journal of lipid research 11 19286648
2025 Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 39950798
2021 Activation of RSK2 upregulates SOX8 to promote methotrexate resistance in gestational trophoblastic neoplasia. Laboratory investigation; a journal of technical methods and pathology 10 34373588
2013 Genome-wide identification of Sox8-, and Sox9-dependent genes during early post-natal testis development in the mouse. Andrology 10 23315995
2007 Sox8 and Sertoli-cell function. Annals of the New York Academy of Sciences 10 17905940
2023 Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development. Reproductive biology and endocrinology : RB&E 9 36631813
2003 Origin and possible roles of the Sox8 transcription factor gene during sexual development. Cytogenetic and genome research 9 14689607
2025 Sox8: a multifaceted transcription factor in development and disease. Biology open 8 39936824
2022 SOX8 promotes cetuximab resistance via HGF/MET bypass pathway activation in colorectal cancer. Cancer chemotherapy and pharmacology 8 35195773
2022 SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway. BioMed research international 8 36246971
2020 The transcription factors SF-1 and SOX8 cooperate to upregulate Cx43 expression in mouse TM4 sertoli cells. Biochemistry and biophysics reports 8 33088929
2010 cDNA cloning and expression analysis of two distinct Sox8 genes in Paramisgurnus dabryanus (Cypriniformes). Journal of genetics 8 20861569
2010 Isolation and expression of two distinct Sox8 genes in mudloach (Misgurnus anguillicaudatus). Biochemical genetics 8 21161367
2009 Evolutionary conserved sequence elements with embryonic enhancer activity in the vicinity of the mammalian Sox8 gene. The international journal of biochemistry & cell biology 8 19638316
2003 Origin and possible roles of the SOX8 transcription factor gene during sexual development. Cytogenetic and genome research 8 14684985
2023 SOX8 is essential for male sexual differentiation in the Chinese soft-shelled turtle Pelodiscus sinensis‡. Biology of reproduction 7 36943308
2022 Regulation of Sox8 through lncRNA Mrhl-Mediated Chromatin Looping in Mouse Spermatogonia. Molecular and cellular biology 7 35412350
2020 The oncogenic role of SOX8 in endometrial carcinoma. Cancer biology & therapy 7 33190587
2019 The evolution and possible role of two Sox8 genes during sex differentiation in Japanese flounder (Paralichthys olivaceus). Molecular reproduction and development 6 30811727
2023 SOX8 promotes tumor growth and metastasis through FZD6-dependent Wnt/β-catenin signaling in colorectal carcinoma. Heliyon 5 38046159
2020 Quantitative Proteomic Profiling Identifies SOX8 as Novel Regulator of Drug Resistance in Gestational Trophoblastic Neoplasia. Frontiers in oncology 5 32411596
2018 Cooperation of Sall4 and Sox8 transcription factors in the regulation of the chicken Sox3 gene during otic placode development. Development, growth & differentiation 5 29520762
2020 Variation analysis of SOX8 gene in Chinese men with non-obstructive azoospermia or oligozoospermia. Andrologia 4 32048324
2024 Transcription Factors Sox8 and Sox10 Contribute with Different Importance to the Maintenance of Mature Oligodendrocytes. International journal of molecular sciences 3 39201442
2023 Biallelic SOX8 Variants Associated With Novel Syndrome With Myopathy, Skeletal Deformities, Intellectual Disability, and Ovarian Dysfunction. Neurology. Genetics 3 38235364
2001 Mouse Sox8 is located between, not within,the t-complex deletions t(w18) and t(h20) on chromosome 17. Cytogenetics and cell genetics 3 11474187
2016 miRNA-124 down-regulates SOX8 expression and suppresses cell proliferation in non-small cell lung cancer [Retraction]. International journal of clinical and experimental pathology 1 29874336
2026 Sox8 and Sox9 regulate differentiation and nuclear positioning of retinal Müller glia. bioRxiv : the preprint server for biology 0 41648182
2026 SOX8 mediates the crosstalk between KRAS and TGF-β pathways to promote the malignant progression of pancreatic cancer. American journal of cancer research 0 41657800
2026 SOX8/CPT2 axis regulates lipid metabolism to support enzalutamide resistance in prostate cancer. Cancer cell international 0 41668040
2026 Exosomal circPOLK promotes metastasis of NSCLC cells via regulating mir-1204/SOX8 axis. Cancer cell international 0 42104439
2026 EphA2/SHP2/SOX8 Axis: A Novel Target for Regulation of Migration and Cetuximab Treatment Sensitivity in Oral Squamous Cell Carcinoma. Molecular carcinogenesis 0 42189834
2025 EHMT1 mediates cellular motility in embryonal rhabdomyosarcoma by activating SOX8 expression. British journal of cancer 0 40467997
2025 TRIM25-Mediated Ubiquitination and Degradation of SOX8 Promotes Ligament Fibroblast Osteogenic Differentiation and Regulates OPLL Progression by Inhibiting OSR2 Transcription. JOR spine 0 40918640
2025 Role of the transcription factor SOX8 in hepatocellular carcinoma development and lymph node metastasis. Translational cancer research 0 40950665
2025 Sox8 is essential for vertebrate gastrulation. EMBO reports 0 41214364
2024 Molecular Analysis of the Differential Activity of Sox8 and Sox10 in Oligodendroglial Cells. International journal of molecular sciences 0 39769160

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