Affinage

Showing NR0B1 — DAX1 is a alias.

NR0B1

Nuclear receptor subfamily 0 group B member 1 · UniProt P51843

Length
470 aa
Mass
51.7 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR0B1/DAX1 is an atypical orphan nuclear receptor that operates as a context-dependent transcriptional regulator coordinating steroidogenesis, gonadal development, and stem cell pluripotency (PMID:9384387, PMID:16466956). In steroidogenic tissues it represses the promoters of StAR, P450scc, 3beta-HSD, and aromatase, blocking both basal and cAMP-stimulated steroid output, largely by binding DNA hairpin structures and antagonizing SF-1 at SF-1 response elements (PMID:9384387, PMID:9751505, PMID:12213901); this repressor function is abolished by AHC-associated missense mutations clustered in the carboxy-terminal ligand-binding domain (PMID:11738790). DAX1 self-associates and partners with other receptors—forming homodimers and DAX1-SHP and DAX1-DAX1A heterodimers through its LXXLL motifs and AF-2 domain, with homodimers dissociating upon engagement of SF-1 or ligand-activated ERalpha (PMID:16709599, PMID:17686645). Rather than acting purely as a repressor, DAX1 can also coactivate SF-1 and LRH-1 target genes through the RNA coactivator SRA and the cofactor TIF2, and its own expression is reciprocally driven by SF-1, LRH-1, Nanog, and Esrrb (PMID:19188450, PMID:20943815, PMID:11923472, PMID:20937355). DAX1 expression and activity are tightly dosage-sensitive in gonadal development: it cooperates with SF-1 to induce Sertoli-cell genes (Dhh, Amh) and is required in both Sertoli and Leydig cells for spermatogenesis and proper aromatase control (PMID:15829514, PMID:11356697, PMID:12606353), and its loss impairs testis differentiation (PMID:12679814). In embryonic stem cells DAX1 maintains pluripotency independently of steroidogenesis by directly repressing the endoderm regulator Gata6 and the 2-cell-stage gene Zscan4c, and it serves as a TRIM66-recruited co-repressor of Dux to suppress the totipotent 2-cell-like state (PMID:25284313, PMID:25772165, PMID:35659877). DAX1 also functions oncogenically: it is the most reproducible EWS/FLI1 target in Ewing's sarcoma, where a direct NR0B1–EWS/FLI protein interaction is required for transformation and co-occupies overlapping genomic targets (PMID:16206264, PMID:17114343, PMID:19920188). A significant pool of DAX1 resides in the cytoplasm associated with polyribosomes and polyadenylated RNA, a post-transcriptional activity also impaired by AHC mutations (PMID:10848616).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1997 High

    Established the core molecular activity of DAX1 by showing it is a sequence-specific transcriptional repressor of steroidogenic genes, defining its biochemical identity beyond an orphan receptor.

    Evidence In vitro DNA binding and reporter assays on the StAR and dax-1 promoters

    PMID:9384387

    Open questions at the time
    • DNA hairpin recognition not structurally resolved
    • no endogenous genome-wide binding map
  2. 1998 High

    Defined the breadth of DAX1's anti-steroidogenic action and its dosage-sensitive antagonism of male sex determination, framing DAX1 as a brake on steroid output and an 'anti-testis' factor.

    Evidence Promoter and steroid-production assays in Y-1 cells; transgenic mouse epistasis against weak Sry alleles

    PMID:9486644 PMID:9751505

    Open questions at the time
    • repressor mechanism on multiple promoters not distinguished (direct DNA vs SF-1 antagonism)
    • the anti-testis model later revised
  3. 1998 High

    Loss-of-function in mice revealed DAX1 is essential for spermatogenesis maintenance independent of hormonal output, separating a tissue role from its endocrine repressor function.

    Evidence Conditional knockout in mice with histology and hormone measurement

    PMID:9843206

    Open questions at the time
    • cell type responsible not yet localized
    • molecular targets in germinal epithelium unknown
  4. 2000 High

    Discovered a non-transcriptional facet of DAX1—cytoplasmic polyribosome and RNA binding—linking it to post-transcriptional regulation and tying this activity to disease alleles.

    Evidence Subcellular fractionation, polyribosome sedimentation, direct RNA binding and AHC mutant analysis

    PMID:10848616

    Open questions at the time
    • specific mRNA targets not identified
    • physiological consequence of RNA binding unresolved
  5. 2001 Medium

    Connected AHC-causing missense mutations to loss of SF-1 repression and mapped them to the C-terminal LBD, establishing a genotype-to-mechanism link for the disease.

    Evidence Transfection reporter assays of patient-derived alleles

    PMID:11738790

    Open questions at the time
    • single-lab transfection data
    • no structural basis for LBD mutation effects
  6. 2001 High

    Cell-type-specific transgenic rescue localized a key reproductive function of DAX1 to Sertoli cells, refining where its activity is required.

    Evidence MIS-promoter human DAX1 transgene rescue in Dax1-null mice with fertility/sperm assays

    PMID:11356697

    Open questions at the time
    • rescue only partial
    • molecular targets in Sertoli cells not defined
  7. 2002 High

    Showed DAX1 represses aromatase via the SF-1 binding site and that SF-1 drives Dax1 expression, establishing a reciprocal SF-1/DAX1 regulatory relationship.

    Evidence Promoter mutagenesis/reporter assays in human stromal cells; transgenic LacZ reporter and SF-1-null embryo analysis

    PMID:11923472 PMID:12213901

    Open questions at the time
    • whether repression requires direct DAX1-DNA contact or only SF-1 tethering unresolved
  8. 2003 High

    Genetic and rescue studies revised the sex-determination model, showing DAX1 promotes rather than opposes testis differentiation and acts in Leydig cells to control aromatase.

    Evidence Targeted knockout gonad analysis; LHR-promoter Leydig-specific transgenic rescue

    PMID:12606353 PMID:12679814

    Open questions at the time
    • mechanistic reconciliation of dosage 'anti-testis' overexpression with loss-of-function pro-testis role incomplete
  9. 2005 High

    Compound-mutant epistasis demonstrated that DAX1 and SF-1 act cooperatively—not antagonistically—to induce Sertoli-cell genes, redefining their relationship in development.

    Evidence Sf1/Dax1 compound mutant mice with staged expression analysis of Dhh, Amh, Cyp17, Cyp11a1

    PMID:15829514

    Open questions at the time
    • direct vs indirect cooperativity at target promoters not dissected
  10. 2006 Medium

    Defined the structural basis of DAX1 dimerization and identified its self- and partner-association via LXXLL/AF-2 modules, explaining how dimer state couples to SF-1/ER engagement.

    Evidence Co-IP, domain mutagenesis, and localization studies of DAX1 homodimers and DAX1-SHP and DAX1-DAX1A heterodimers

    PMID:16709599 PMID:17686645

    Open questions at the time
    • single-lab co-IP without structure
    • functional output of each dimer species not separated
  11. 2006 Medium

    Revealed a steroidogenesis-independent role in maintaining the undifferentiated state of ES cells, expanding DAX1's biology into pluripotency.

    Evidence siRNA and conditional knockout in ES cells with differentiation assays

    PMID:16466956

    Open questions at the time
    • direct target genes not yet identified at this stage
    • single-lab
  12. 2006 Medium

    Mapped a hinge-region mutation (C200W) that mislocalizes DAX1 to cytoplasm and abolishes repression, implicating SF-1-independent nuclear import in its activity.

    Evidence Immunohistochemistry, repression assays, and in vitro interaction assays of the C200W mutant

    PMID:16459121

    Open questions at the time
    • the import factor responsible not identified
    • single-lab
  13. 2006 High

    Identified NR0B1 as a critical, reproducibly upregulated EWS/FLI1 target required for the transformed phenotype in Ewing's sarcoma, opening an oncogenic dimension.

    Evidence Inducible EWS/FLI1 expression, RNAi silencing, and transformation assays across multiple Ewing cell lines

    PMID:16206264 PMID:17114343

    Open questions at the time
    • mechanism of NR0B1 contribution to transformation not yet defined at this stage
  14. 2006 Medium

    Cross-species work placed dax1 downstream of SF-1 (ff1b) in regulating the adrenal-equivalent interrenal organ and its steroidogenic genes.

    Evidence Morpholino knockdown and in situ hybridization in zebrafish

    PMID:16840536

    Open questions at the time
    • morpholino specificity caveats
    • single-lab
  15. 2009 High

    Reframed DAX1 as a dosage-dependent coactivator, not just a repressor, by linking it to the RNA coactivator SRA and TIF2 to activate SF-1 targets.

    Evidence Co-IP, reporter assays, SRA/Dax-1 knockdown, live-cell imaging, and disease-mutation analysis in adrenal/Leydig cells

    PMID:19188450

    Open questions at the time
    • determinants switching DAX1 between repressor and coactivator modes unresolved
  16. 2009 High

    Established a direct NR0B1–EWS/FLI protein interaction required for transformation and showed genome-wide co-occupancy, providing the mechanistic link for DAX1's oncogenic role.

    Evidence Co-IP, ChIP, transcriptional profiling, and interaction-defective mutant rescue in Ewing cells

    PMID:19920188

    Open questions at the time
    • how the interaction reshapes EWS/FLI transcriptional output mechanistically not fully defined
  17. 2009 Medium

    Extended DAX1's oncogenic relevance beyond Ewing's sarcoma to lung adenocarcinoma cancer-stem-cell function and to a neuronal RA/PI3K-Akt-nNOS axis, indicating broad context-specific roles.

    Evidence Side-population assay, RNAi, invasion/colony/xenograft assays in lung adenocarcinoma; pathway inhibition and knockdown/overexpression in neuroblastoma

    PMID:19644015 PMID:19726747

    Open questions at the time
    • direct DAX1 targets in these contexts incompletely defined
    • single-lab each
  18. 2010 High

    Demonstrated context-switched coactivation in ES cells, where DAX1 complexes with LRH-1 to activate Oct4 via SRA, and that LRH-1/Nanog reciprocally drive Dax1, embedding it in the pluripotency network.

    Evidence Co-IP, ChIP, EMSA, reporter assays, and SRA/factor knockdown in mouse ES cells

    PMID:20937355 PMID:20943815

    Open questions at the time
    • what dictates LRH-1 coactivation vs SF-1 repression unresolved
  19. 2013 Medium

    Positioned DAX1 within a competitive regulatory loop with Esrrb and Oct3/4, repressing Esrrb activity while being reciprocally regulated, refining pluripotency circuit logic.

    Evidence Co-IP with domain mapping, EMSA, reporter assays, and OE/KD in ES cells

    PMID:23508100

    Open questions at the time
    • single-lab
    • in vivo relevance of the loop not tested
  20. 2014 High

    Defined a direct molecular mechanism for pluripotency maintenance—DAX1 represses Gata6 to block extra-embryonic endoderm—acting in parallel with Nanog.

    Evidence Stable/inducible knockdown, overexpression, LIF-withdrawal, Gata6 reporter, and reprogramming assays

    PMID:25284313

    Open questions at the time
    • genome-wide direct target set not fully enumerated
  21. 2015 Medium

    Identified Zscan4c as a direct DAX1-repressed 2-cell-stage gene whose derepression causes proliferation defects, linking DAX1 to control of the totipotency program.

    Evidence Inducible knockout in ES cells, transcriptome analysis, and direct promoter repression assay

    PMID:25772165

    Open questions at the time
    • single-lab
    • relationship to other 2C regulators not fully mapped
  22. 2017 High

    Showed SF-1 SUMOylation enhances DAX1 recruitment to drive repression of the fetal adrenal enhancer, providing a PTM-controlled mechanism for fetal adrenal X-zone regression.

    Evidence In vitro binding, FAdE-LacZ reporter mice, SUMO-deficient Sf1 knock-in and Dax1-knockout mice

    PMID:28893949

    Open questions at the time
    • how SUMOylation alters the SF-1/DAX1 interface structurally unknown
  23. 2018 Medium

    Demonstrated a pro-oncogenic mechanism in cervical cancer where DAX1 directly represses GSK3beta to activate Wnt/beta-catenin signaling, expanding its tumor-promoting repertoire.

    Evidence RNAi, TOP/FOP-Flash Wnt reporter, ChIP, dual-luciferase, and GSK3beta rescue

    PMID:29497051

    Open questions at the time
    • single-lab
    • in vivo confirmation limited
  24. 2022 High

    Provided structural and functional mechanism for DAX1 as a TRIM66-recruited co-repressor of Dux, showing how it suppresses the totipotent 2-cell-like state via a chromatin-reading module.

    Evidence Co-IP, ChIP, crystal structure of TRIM66 PHD finger, PHD mutagenesis, and chimeric embryo/Dux reporter assays

    PMID:35659877

    Open questions at the time
    • DAX1's own contribution to repressive complex assembly not structurally resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular determinant that switches DAX1 between transcriptional repressor and coactivator across steroidogenic, pluripotency, and oncogenic contexts remains undefined.
  • no structural model of DAX1 DNA/hairpin or coactivator binding
  • the natural ligand (if any) and its role in mode-switching unknown
  • no unified rule predicting repressor vs coactivator output by partner/context

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 4 GO:0005634 nucleus 3 GO:0005840 ribosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 2
Partners
ESRRBEWSR1-FLI1NR0B2NR5A1NR5A2TIF2TRIM66

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 DAX-1 binds DNA hairpin structures and acts as a transcriptional repressor of the StAR (steroidogenic acute regulatory protein) gene promoter, blocking steroid production in vitro and in vivo. DAX-1 binding sites were identified in the promoters of the dax-1 and StAR genes. In vitro DNA binding assays, transcriptional reporter assays (in vitro and in vivo), promoter analysis Nature High 9384387
1998 DAX-1 blocks steroid production at multiple levels by repressing StAR, P450scc, and 3beta-HSD promoter activities in adrenocortical Y-1 cells, impairing both basal and cAMP-stimulated steroid production without affecting the PKA pathway. Cell line expression (Y-1 cells), steroid production assays, promoter activity assays, cAMP pathway analysis Endocrinology High 9751505
1998 Dax1 antagonizes Sry action in mammalian sex determination; XY mice carrying extra copies of Dax1 show delayed testis development, and sex reversal occurs when the transgene is tested against weak Sry alleles, establishing a dosage-sensitive genetic epistasis between Dax1 and Sry. Transgenic mouse overexpression, genetic epistasis with weak Sry alleles Nature High 9486644
1998 Loss of Ahch/Dax1 in male mice causes progressive degeneration of the testicular germinal epithelium and male sterility independent of abnormalities in gonadotropin and testosterone production, establishing Dax1 as essential for spermatogenesis maintenance. Female Ahch-null mice have normal ovarian development and fertility. Cre-mediated conditional gene knockout in mice, histological analysis, hormone measurement Nature genetics High 9843206
2000 DAX-1 protein is found both in the nucleus and cytoplasm; a significant proportion associates with polyribosomes and binds polyadenylated RNA. Two domains within DAX-1 mediate cooperative RNA binding. AHC-causing mutations significantly impair RNA binding, suggesting a post-transcriptional regulatory role. Subcellular fractionation, polyribosome sedimentation, RNA binding assays (direct), mutational analysis of AHC alleles Molecular and cellular biology High 10848616
2001 AHC-associated DAX1 missense mutations abrogate its ability to act as a transcriptional repressor of SF-1, as demonstrated in transfection assays. All missense mutations are located within the carboxy-terminal half of the protein (putative ligand binding domain). Transfection reporter assays, mutational analysis of patient-derived alleles Molecular and cellular endocrinology Medium 11738790
2001 Sertoli cell-specific expression of a human DAX1 transgene (MIS promoter) partially rescued fertility in Dax1-deficient male mice, restoring sperm motility, epididymal sperm count, and in vitro fertilization capacity, establishing that Dax1 function in Sertoli cells is sufficient to overcome key thresholds for sperm production. Transgenic rescue in Dax1-knockout mice with cell type-specific promoter, fertility assays, sperm function assays Endocrinology High 11356697
2002 DAX-1 inhibits cAMP/SF-1-mediated aromatase P450 (P450arom) promoter activity in a dose-dependent manner in cultured human endometriotic and endometrial stromal cells; site-directed disruption of the SF-1 binding site in the P450arom promoter abolishes this effect, indicating DAX-1 acts through the SF-1 binding site. Transient transfection reporter assays, site-directed mutagenesis of promoter, human primary cell cultures The Journal of clinical endocrinology and metabolism Medium 12213901
2002 Dax1 expression in the developing gonad is regulated by steroidogenic factor 1 (SF-1) via a conserved SF-1 consensus-binding site located ~4 kb upstream of the Dax1 start codon; Dax1 expression is greatly reduced in SF-1-deficient gonads. Transgenic reporter (LacZ) mouse assay, site-directed mutagenesis of SF-1 binding site, analysis of SF-1-null embryos Molecular endocrinology High 11923472
2003 Leydig cell-specific expression of DAX1 (LHR promoter transgene) in Dax1-knockout mice restores aromatase expression to normal levels and increases sperm production, establishing that Dax1 function in Leydig cells contributes to testicular function and that Dax1 deficiency in Leydig cells underlies aromatase overexpression. Transgenic rescue with Leydig cell-specific promoter in Dax1-knockout background, aromatase expression analysis, sperm counting Biology of reproduction High 12606353
2003 Nr0b1/Dax1 is required for testis differentiation; loss of Nr0b1 in mice impairs rather than promotes testis formation, contradicting the earlier 'anti-testis' model and instead supporting a pro-testis role. Targeted gene knockout in mice, gonadal development analysis Nature genetics High 12679814
2005 In the developing testis, Sf1 and Dax1 function cooperatively (not antagonistically) to induce Dhh and Amh expression in Sertoli cells; double mutant Sf1/Dax1 gonads show reduced Dhh undetectable by E11.5, more severe than either single mutant, while Cyp17 and Cyp11a1 (fetal Leydig markers) are further reduced in double mutants compared to Sf1 heterozygotes alone. Genetic epistasis using compound mutant mice (Sf1 heterozygous × Dax1-null), gene expression analysis at defined embryonic stages Development High 15829514
2006 NR0B1 expression is required for the oncogenic/transformed phenotype of Ewing's sarcoma cells; retroviral-mediated RNAi knockdown of NR0B1 in patient-derived Ewing's sarcoma cell lines abolishes the transformed phenotype. NR0B1 is the most reproducibly upregulated EWS/FLI target gene across three Ewing's sarcoma lines. Retroviral RNAi knockdown in patient-derived cell lines, transcriptional profiling, functional transformation assays Molecular cancer research High 17114343
2006 DAX1 (NR0B1) is specifically upregulated by the EWS/FLI1 fusion oncoprotein (not by wild-type FLI1) in 293 cells and Ewing tumor cells; siRNA silencing of EWS/FLI1 in a Ewing cell line markedly reduces DAX1 mRNA and protein, confirming direct dependence on EWS/FLI1. cDNA arrays with inducible EWS/FLI1 expression, RNAi silencing, RT-PCR, immunoblot International journal of cancer High 16206264
2006 Zebrafish dax1 functions downstream of ff1b (SF-1) in regulating the interrenal organ (adrenal cortex equivalent); dax1 morpholino knockdown downregulates steroidogenic genes cyp11a and star, and ff1b morpholino abolishes dax1 expression in the interrenal organ, while dax1 morpholino does not affect ff1b expression. Morpholino oligonucleotide knockdown in zebrafish, whole-mount in situ hybridization, gene expression analysis Molecular endocrinology Medium 16840536
2006 DAX1 forms homodimers in both nucleus and cytoplasm; homodimerization involves an interaction between DAX1 amino and carboxy termini through LXXLL motifs and the AF-2 domain. DAX1 homodimers dissociate upon heterodimerization with SF-1 or ligand-activated ERα. DAX1-SHP heterodimers also form in the nucleus via LXXLL motifs and AF-2 domain. Co-immunoprecipitation in mammalian cells, subcellular localization studies, domain-deletion and mutagenesis analysis Molecular endocrinology Medium 16709599
2006 Dax1 has a novel role in maintaining a relatively undifferentiated state in early embryogenesis; siRNA knockdown of Nr0b1 in embryonic stem cells causes differentiation toward endoderm-like fate, and conditional knockout of Nr0b1 in ES cells leads to differentiation, indicating Nr0b1 maintains pluripotency independent of steroidogenesis. siRNA knockdown in ES cells, Cre-mediated conditional knockout in ES cells, differentiation assays Molecular genetics and metabolism Medium 16466956
2009 Dax-1 can function as a dosage-dependent coactivator of SF-1 target genes (rather than solely as a repressor). Both SF-1 and Dax-1 bind the RNA coactivator SRA; TIF2 associates with Dax-1 and synergistically coactivates SF-1 targets. Knockdown of endogenous Dax-1 downregulates CYP11A1 and StAR expression in adrenal and Leydig cells. A naturally occurring Dax-1 mutation inhibits this coactivation and mislocalizes the Dax-1/TIF2 complex. Co-immunoprecipitation, luciferase reporter assays, siRNA knockdown of SRA and Dax-1, live-cell imaging of protein localization, patient mutation analysis Molecular and cellular biology High 19188450
2009 NR0B1 and EWS/FLI physically interact; this protein-protein interaction is required for oncogenic transformation of Ewing's sarcoma cells. NR0B1 mutations that disrupt the interaction have transcriptional consequences and abrogate oncogenic transformation. Genome-wide ChIP shows NR0B1 and EWS/FLI co-localize at overlapping genomic targets. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transcriptional profiling, transformation assays with NR0B1 interaction-defective mutants Cancer research High 19920188
2009 DAX1 (NR0B1) is expressed in cancer stem cell-enriched side population of lung adenocarcinoma; NR0B1 knockdown reduces invasion, colony formation, and tumorigenicity in NOD/SCID mice, establishing a functional role in lung adenocarcinoma malignancy. Hoechst dye exclusion (side population assay), RNAi knockdown, in vitro invasion and colony assays, xenograft tumorigenicity assay The American journal of pathology Medium 19644015
2010 In mouse ES cells, Dax1 forms a complex with LRH-1 (Nr5a2) demonstrated by co-immunoprecipitation. Contrary to its repressor role in steroidogenic cells, Dax1 accentuates LRH-1-mediated activation of the Oct4 gene; Dax1 is localized to the Oct4 promoter at the LRH-1 binding site by ChIP. This coactivation is dependent on the RNA coactivator SRA. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), luciferase reporter assays with Dax1 overexpression/knockdown, SRA knockdown Molecular endocrinology High 20943815
2010 LRH-1 binds the -128 site of the Dax1 promoter to regulate its expression in mouse ES cells; Nanog binds an intronic site of Dax1 and enhances transcription. Overexpression and knockdown of both LRH-1 and Nanog alter Dax1 expression, establishing cooperative transcriptional regulation of Dax1 in ES cells. Luciferase reporter assays, EMSA, chromatin immunoprecipitation, overexpression and knockdown experiments Molecular and cellular endocrinology Medium 20937355
2013 Dax1 interacts with the orphan nuclear receptor Esrrb through DAX1 LXXLL motifs and Esrrb activation/ligand-binding domains. Dax1 represses Esrrb transcriptional activity. Esrrb also directly binds the Dax1 promoter (ERRE1 site) to enhance Dax1 expression in an Oct3/4-independent manner. Oct3/4, Dax1, and Esrrb exhibit competitive inhibitory interactions forming a regulatory loop. Co-immunoprecipitation, luciferase reporter assays, EMSA/direct binding assays, overexpression and knockdown in ES cells Molecular and cellular biology Medium 23508100
2014 Dax1 acts in parallel with Nanog to maintain mouse ES cell identity; Dax1 overexpression supports LIF-independent self-renewal; Dax1 stable knockdown predisposes mESCs towards differentiation. Dax1 is indispensable for self-renewal of Nanog-low mESCs. Dax1 prevents extra-embryonic endoderm commitment by directly repressing Gata6 transcription. Stable knockdown, overexpression, inducible knockdown, LIF-withdrawal assay, luciferase/reporter assays for Gata6 repression, reprogramming assays Nature communications High 25284313
2015 Nr0b1 (Dax1)-null mouse ES cells are viable and pluripotent but exhibit slow proliferation and overexpression of 2-cell-stage transcripts including Zscan4c. Nr0b1 directly represses the Zscan4c promoter; overexpression of Zscan4c causes G2 arrest and cell death, explaining the proliferation defect. Inducible Cre-loxP knockout in ES cells, chimera assay for pluripotency, transcriptome analysis, direct promoter repression assay Scientific reports Medium 25772165
2016 nr0b1 mutation in zebrafish causes female-to-male sex reversal through reduced cell proliferation and abnormal somatic cell differentiation in gonads at the undifferentiated and bi-potential ovary stages, without increasing apoptosis (Caspase-3, tp53-independent mechanism). CRISPR/ENU-generated heritable nr0b1 mutations in zebrafish, histological analysis, cell proliferation assays, genetic epistasis with tp53 mutation Molecular and cellular endocrinology Medium 27267667
2017 Sf1 SUMOylation enhances binding of Dax1 to Sf1, which further enhances transcriptional repression of the fetal adrenal enhancer (FAdE). In vivo, both SUMOylation-deficient Sf1 and Dax1-knockout mice show delayed regression of the postnatal fetal adrenal cortex (X-zone), with FAdE expression retained in postnatal X-zone cells. In vitro binding assays, transgenic reporter mouse models (FAdE-LacZ), Sf1 SUMOylation-deficient knock-in mice, Dax1-knockout mice Development High 28893949
2018 DAX1 promotes cervical cancer cell growth and tumorigenicity by transcriptionally repressing GSK3β (an inhibitor of Wnt/β-catenin) through direct binding to the -666~-444 region of the GSK3β promoter, as confirmed by dual-luciferase reporter and ChIP assays, leading to activation of Wnt/β-catenin signaling and upregulation of cyclinD1 and c-myc. RNAi knockdown, TOP/FOP-Flash Wnt reporter assay, ChIP assay, dual-luciferase reporter assay, GSK3β pharmacological rescue Cell death & disease Medium 29497051
2022 TRIM66 recruits DAX1 as a co-repressor to the Dux promoter to suppress the totipotent 2-cell-like state in mESCs. TRIM66's repressive effect on Dux is dependent on DAX1. Crystal structure shows TRIM66's PHD finger recognizes H3K4-K9me3; mutations in the PHD finger abolish Dux repression. Co-IP, ChIP, crystal structure determination, mutagenesis of PHD finger, chimeric embryo assays, Dux reporter assays Cell stem cell High 35659877
2006 A missense mutation in the hinge region of DAX1 (C200W) shifts subcellular localization from nucleus to cytoplasm and impairs transcriptional repression activity. Nuclear import of DAX1 involves a direct interaction with SF-1; the C200W mutant retains ability to interact with SF-1 in vitro, suggesting SF-1-independent interactions are responsible for the import defect. Immunohistochemistry of transfected cells, transcriptional repression assays, in vitro interaction assays Molecular genetics and metabolism Medium 16459121
2009 Retinoic acid (RA)-induced nNOS transcription in human neuroblastoma TGW-nu-I cells requires DAX1 (NR0B1) as a critical mediator; RA increases DAX1 expression via PI3K/Akt signaling, and upregulation of DAX1 in turn induces nNOS transcription. DAX1 knockdown blocks RA-induced nNOS expression, identifying nNOS as a DAX1 target gene in this pathway. Pharmacological inhibition of PI3K/Akt, DAX1 overexpression and knockdown, transcriptional reporter/RT-PCR assays in human neuroblastoma cells American journal of physiology. Cell physiology Medium 19726747
2007 LXXLL motifs and AF-2 domain of SHP mediate SHP homodimerization and DAX1-SHP heterodimerization. DAX1 LXXLL motifs are redundant for DAX1 homodimerization. DAX1A (alternatively spliced isoform) localizes predominantly to cytoplasm but forms DAX1-DAX1A heterodimers in the nucleus, with AF-2 domain of DAX1 required for this interaction. Co-immunoprecipitation, domain deletion and mutagenesis, subcellular localization analysis Molecular genetics and metabolism Medium 17686645

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Investigating intestinal inflammation in DSS-induced model of IBD. Journal of visualized experiments : JoVE 540 22331082
1998 Dax1 antagonizes Sry action in mammalian sex determination. Nature 396 9486644
1998 Role of Ahch in gonadal development and gametogenesis. Nature genetics 341 9843206
1997 DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis. Nature 337 9384387
1996 Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function. Nature genetics 308 8630494
2000 SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development. Mechanisms of development 205 10704874
2006 NR0B1 is required for the oncogenic phenotype mediated by EWS/FLI in Ewing's sarcoma. Molecular cancer research : MCR 173 17114343
2004 Molecular mechanisms of DAX1 action. Molecular genetics and metabolism 159 15464421
2015 DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best practice & research. Clinical endocrinology & metabolism 156 26303087
2014 Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization. Cellular & molecular immunology 150 24727542
1998 DAX-1 blocks steroid production at multiple levels. Endocrinology 149 9751505
2003 Dax1 is required for testis determination. Nature genetics 129 12679814
2001 Phenotypic spectrum of mutations in DAX-1 and SF-1. Molecular and cellular endocrinology 105 11738790
2013 Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway. American journal of physiology. Gastrointestinal and liver physiology 104 24232001
2020 Cow and Human Milk-Derived Exosomes Ameliorate Colitis in DSS Murine Model. Nutrients 100 32858892
2000 Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA. Molecular and cellular biology 99 10848616
2009 Dax-1 and steroid receptor RNA activator (SRA) function as transcriptional coactivators for steroidogenic factor 1 in steroidogenesis. Molecular and cellular biology 91 19188450
2000 Temperature-dependent sex determination in the American alligator: expression of SF1, WT1 and DAX1 during gonadogenesis. Gene 87 10675033
2013 Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis. PloS one 83 23861820
2006 Novel role for the orphan nuclear receptor Dax1 in embryogenesis, different from steroidogenesis. Molecular genetics and metabolism 82 16466956
2001 Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita. Human mutation 77 11748841
2009 EWS/FLI and its downstream target NR0B1 interact directly to modulate transcription and oncogenesis in Ewing's sarcoma. Cancer research 76 19920188
2020 Melatonin Alleviates Neuroinflammation and Metabolic Disorder in DSS-Induced Depression Rats. Oxidative medicine and cellular longevity 68 32802257
2015 CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH. Human molecular genetics 68 26464492
2005 Nuclear receptors Sf1 and Dax1 function cooperatively to mediate somatic cell differentiation during testis development. Development (Cambridge, England) 67 15829514
2006 The orphan nuclear receptor DAX1 is up-regulated by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors. International journal of cancer 66 16206264
2005 DAX1 origin, function, and novel role. Molecular genetics and metabolism 61 16146703
2022 Atractylodes lancea Rhizoma Attenuates DSS-Induced Colitis by Regulating Intestinal Flora and Metabolites. The American journal of Chinese medicine 57 35114907
2018 DAX1 promotes cervical cancer cell growth and tumorigenicity through activation of Wnt/β-catenin pathway via GSK3β. Cell death & disease 56 29497051
2002 WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells. The Journal of clinical endocrinology and metabolism 55 12213901
1999 Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay. The Journal of clinical endocrinology and metabolism 55 10599708
2011 Hypogonadotropic hypogonadism in subjects with DAX1 mutations. Molecular and cellular endocrinology 54 21672607
2017 Aryl hydrocarbon receptor inhibits inflammation in DSS‑induced colitis via the MK2/p‑MK2/TTP pathway. International journal of molecular medicine 53 29207040
2004 Sex determination: a 'window' of DAX1 activity. Trends in endocrinology and metabolism: TEM 53 15046740
2007 DAX1: Increasing complexity in the roles of this novel nuclear receptor. Molecular and cellular endocrinology 51 17210221
2014 Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency. Nature communications 50 25284313
2007 Dax1 suppresses P450arom expression in medaka ovarian follicles. Molecular reproduction and development 50 17342735
2014 The oxysterol receptor LXRβ protects against DSS- and TNBS-induced colitis in mice. Mucosal immunology 49 24803164
2000 Cloning and expression of a DAX1 homologue in the chicken embryo. Journal of molecular endocrinology 49 10656994
2009 Clinical and genetic heterogeneity of congenital adrenal hypoplasia due to NR0B1 gene mutations. Clinical endocrinology 48 19508677
2002 Molecular cloning of DAX1 and SHP cDNAs and their expression patterns in the Nile tilapia, Oreochromis niloticus. Biochemical and biophysical research communications 48 12270141
2021 Anthocyanin-containing purple potatoes ameliorate DSS-induced colitis in mice. The Journal of nutritional biochemistry 45 33705951
2010 Dax1 up-regulates Oct4 expression in mouse embryonic stem cells via LRH-1 and SRA. Molecular endocrinology (Baltimore, Md.) 44 20943815
2002 Dax1 expression is dependent on steroidogenic factor 1 in the developing gonad. Molecular endocrinology (Baltimore, Md.) 42 11923472
2024 Puerarin ameliorates colitis by direct suppression of macrophage M1 polarization in DSS mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 41 39326132
2016 Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3. Journal of molecular medicine (Berlin, Germany) 41 27709266
2007 The expression of nr0b1 and nr5a4 during gonad development and sex change in protandrous black porgy fish, Acanthopagrus schlegeli. Biology of reproduction 39 17959853
1999 DAX-1, an 'antitestis' gene. Cellular and molecular life sciences : CMLS 39 10412368
2003 DAX1 and its network partners: exploring complexity in development. Molecular genetics and metabolism 38 14567960
2001 Sertoli cell-specific rescue of fertility, but not testicular pathology, in Dax1 (Ahch)-deficient male mice. Endocrinology 38 11356697
2010 Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function. Endocrine development 37 21164257
2003 Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 37 14689056
2022 Intestinal Epithelial AMPK Deficiency Causes Delayed Colonic Epithelial Repair in DSS-Induced Colitis. Cells 36 35203241
2016 nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation. Molecular and cellular endocrinology 36 27267667
1998 The Role of DAX-1 in Reproduction. Trends in endocrinology and metabolism: TEM 36 18406261
2024 Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis. Redox biology 34 38330550
2015 Nr0b1 is a negative regulator of Zscan4c in mouse embryonic stem cells. Scientific reports 34 25772165
2006 Zebrafish dax1 is required for development of the interrenal organ, the adrenal cortex equivalent. Molecular endocrinology (Baltimore, Md.) 34 16840536
1999 Novel DAX1 mutations in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism. Clinical endocrinology 34 10341858
2014 Clinical and biochemical function of polymorphic NR0B1 GGAA-microsatellites in Ewing sarcoma: a report from the Children's Oncology Group. PloS one 32 25093581
2006 DAX1 and X-linked adrenal hypoplasia congenita: clinical and molecular analysis in five patients. European journal of endocrinology 31 16645015
2013 Dax1 associates with Esrrb and regulates its function in embryonic stem cells. Molecular and cellular biology 30 23508100
2009 Tumorigenic role of orphan nuclear receptor NR0B1 in lung adenocarcinoma. The American journal of pathology 30 19644015
2004 Nr0b1 and its network partners are expressed early in murine embryos prior to steroidogenic axis organogenesis. Gene expression patterns : GEP 30 14678822
2018 Inhibition of NADPH oxidase activities ameliorates DSS-induced colitis. Biochemical pharmacology 28 30321511
2006 Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers. Molecular endocrinology (Baltimore, Md.) 28 16709599
2015 Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis. Genetics and molecular research : GMR 27 25966111
2010 LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells. Molecular and cellular endocrinology 27 20937355
2003 Leydig cell-specific expression of DAX1 improves fertility of the Dax1-deficient mouse. Biology of reproduction 27 12606353
2009 Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cells. American journal of physiology. Cell physiology 26 19726747
2010 Targeting DAX-1 in embryonic stem cells and cancer. Expert opinion on therapeutic targets 25 20055716
2022 Gpr174 Knockout Alleviates DSS-Induced Colitis via Regulating the Immune Function of Dendritic Cells. Frontiers in immunology 24 35669778
2023 Geniposidic acid attenuates DSS-induced colitis through inhibiting inflammation and regulating gut microbiota. Phytotherapy research : PTR 23 37098758
2022 A TRIM66/DAX1/Dux axis suppresses the totipotent 2-cell-like state in murine embryonic stem cells. Cell stem cell 23 35659877
2008 Nuclear receptor DAX1 in human prostate cancer: a novel independent biological modulator. Endocrine journal 23 18827407
1996 Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus. Gene 23 8921887
2020 miR-142-5p/DAX1-dependent regulation of P450c17 contributes to triclosan-mediated testosterone suppression. The Science of the total environment 22 32084696
2004 NR0B1A: an alternatively spliced form of NR0B1. Molecular genetics and metabolism 22 15589120
2019 Electroacupuncture and Moxibustion Improved Anxiety Behavior in DSS-Induced Colitis Mice. Gastroenterology research and practice 21 30881446
2024 FMT rescues mice from DSS-induced colitis in a STING-dependent manner. Gut microbes 20 39324491
2017 Timing of adrenal regression controlled by synergistic interaction between Sf1 SUMOylation and Dax1. Development (Cambridge, England) 20 28893949
2000 Primate DAX1, SRY, and SOX9: evolutionary stratification of sex-determination pathway. American journal of human genetics 20 11112659
2006 A familial missense mutation in the hinge region of DAX1 associated with late-onset AHC in a prepubertal female. Molecular genetics and metabolism 19 16459121
2022 Dietary lactate supplementation can alleviate DSS-induced colitis in piglets. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 36580723
2019 MLKL deficiency inhibits DSS-induced colitis independent of intestinal microbiota. Molecular immunology 18 30738250
2011 Expression of nuclear receptor DAX-1 and androgen receptor in human breast cancer. Journal of surgical oncology 18 21240988
1997 Porcine Dax-1 gene: isolation and expression during gonadal development. Molecular and cellular endocrinology 18 9453240
2024 Magnolin alleviated DSS-induced colitis by inhibiting ALOX5-mediated ferroptosis. The Kaohsiung journal of medical sciences 17 38340032
2023 Aminosalicylates target GPR35, partly contributing to the prevention of DSS-induced colitis. European journal of pharmacology 17 37054942
2009 X-linked congenital adrenal hypoplasia with hypogonadotropic hypogonadism caused by an inversion disrupting a conserved noncoding element upstream of the NR0B1 (DAX1) gene. The Journal of clinical endocrinology and metabolism 17 19773398
2024 Lacticaseibacillusparacasei BNCC345679 revolutionizes DSS-induced colitis and modulates gut microbiota. Frontiers in microbiology 16 38601942
2022 Polydatin alleviates DSS- and TNBS-induced colitis by suppressing Th17 cell differentiation via directly inhibiting STAT3. Phytotherapy research : PTR 16 35766233
2018 Constitutive androstane receptor and pregnane X receptor cooperatively ameliorate DSS-induced colitis. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 16 30442521
2022 Baicalin Ameliorates DSS-Induced Colitis by Protecting Goblet Cells through Activating NLRP6 Inflammasomes. Evidence-based complementary and alternative medicine : eCAM 15 36016685
2022 Cysteine protease of Clonorchis sinensis alleviates DSS-induced colitis in mice. PLoS neglected tropical diseases 15 36084127
2005 Thirteen novel mutations in the NR0B1 (DAX1) gene as cause of adrenal hypoplasia congenita. Human mutation 15 15841486
2023 Investigation of Flavonoid Scaffolds as DAX1 Inhibitors against Ewing Sarcoma through Pharmacoinformatic and Dynamic Simulation Studies. International journal of molecular sciences 14 37298283
2015 Molecular cloning and sexually dimorphic expression patterns of nr0b1 and nr5a2 in olive flounder, Paralichthys olivaceus. Development genes and evolution 14 25758177
2014 Ron receptor signaling is protective against DSS-induced colitis in mice. American journal of physiology. Gastrointestinal and liver physiology 14 24742989
2007 LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1 (NR0B1)-DAX1A heterodimerization. Molecular genetics and metabolism 14 17686645

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