Affinage

ATOH8

Transcription factor ATOH8 · UniProt Q96SQ7

Length
321 aa
Mass
34.6 kDa
Annotated
2026-06-09
40 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATOH8 is a basic helix-loop-helix transcription factor that operates downstream of BMP-SMAD and TGF-β signaling to constrain cellular plasticity, differentiation, and metabolic programs across multiple tissues (PMID:31719172, PMID:36626550, PMID:36075976). It lacks a canonical transactivation domain and carries intrinsic repressor activity dependent on a conserved proline-rich domain; it binds the ubiquitous E protein E47 and quenches E47- and Neurogenin3-driven transcription (PMID:23938248). ATOH8 acts directly on chromatin through E-box recognition—activating HAMP (hepcidin) and the eNOS promoter (PMID:24236640, PMID:24463812) and an ATOH8-V1 isoform activating RhoC (PMID:33049034)—while functioning as a repressor at cell-cycle, stemness, and metabolic loci by partnering with sequence- and signal-specific cofactors: SMAD3 to drive oncogene-induced senescence and restrain Ras-driven lung tumorigenesis (PMID:36626550), Runx2 to lower the Rankl/Opg ratio and suppress osteoclastogenesis (PMID:32923015), and TCF3 to repress SCD and sensitize tumor cells to ferroptosis (PMID:40133667). It also binds and destabilizes HIF-2α, and Atoh8-deficient mice develop a pulmonary arterial hypertension-like phenotype (PMID:31719172). In cancer, ATOH8 represses stem-cell genes OCT4, NANOG, and CD133 to limit hepatocellular tumor-initiating properties (PMID:26099525), and its nuclear translocation is promoted by calcineurin (PPP3CB), after which it represses Sp1 to suppress pancreatic cancer metastasis (PMID:40222712). ATOH8 itself is a tightly controlled node: it is transcriptionally silenced by EZH2-mediated H3K27me3 and promoter DNA methylation (PMID:30786928, PMID:40133667), destabilized post-transcriptionally by FXR1 binding its 3'UTR (PMID:39511680) and by WTAP-dependent m6A modification (PMID:40399698). Beyond transcriptional repression, ATOH8 binds autophagosome-assembly genes and promotes autophagic flux (PMID:41440013).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2010 Low

    Established that Atoh8 is developmentally required for tissue patterning, providing the first in vivo phenotype linking the factor to retinal lamination and muscle fiber differentiation.

    Evidence Morpholino knockdown in zebrafish with in situ hybridization and histology

    PMID:20532172

    Open questions at the time
    • Morpholino phenotypes not confirmed by genetic mutant or rescue
    • No molecular target or mechanism identified
    • Direct transcriptional activity not addressed
  2. 2013 High

    Defined ATOH8 as a direct E-box-binding transcription factor and resolved its dual regulatory logic—direct HAMP activation versus intrinsic repressor activity at E47-dependent targets.

    Evidence ChIP, reporter mutagenesis, domain deletion, and Co-IP in hepatic and pancreatic cell models

    PMID:23938248 PMID:24236640

    Open questions at the time
    • Did not reconcile when ATOH8 activates versus represses a given locus
    • Cofactor selection rules unresolved
    • No structural basis for the proline-rich repressor domain
  3. 2014 Medium

    Connected ATOH8 to mechanotransduction by showing it is shear-stress-responsive and directly activates eNOS to drive endothelial differentiation.

    Evidence hESC-to-endothelial induction with eNOS reporter assays and zebrafish/mouse in situ hybridization

    PMID:24463812

    Open questions at the time
    • Single lab
    • Upstream sensor coupling shear stress to ATOH8 not defined
    • Direct binding to eNOS promoter shown by reporter but not ChIP in this study
  4. 2015 High

    Identified ATOH8 as a tumor suppressor that represses stem-cell genes (OCT4, NANOG, CD133), explaining how its loss enables cancer stem-cell properties.

    Evidence EMSA, reporter assays, overexpression/knockdown, and xenografts in HCC cell lines

    PMID:26099525

    Open questions at the time
    • Cofactors at stemness promoters not identified
    • Whether repression is direct at all three loci not fully resolved
  5. 2019 High

    Placed ATOH8 in the BMP-SMAD1/5 axis as a direct target and identified HIF-2α as a protein partner whose abundance it lowers, linking ATOH8 to hypoxia signaling and pulmonary vascular homeostasis.

    Evidence Co-IP, reporter assays, knockout mice with hemodynamics, and zebrafish

    PMID:31719172

    Open questions at the time
    • Mechanism by which ATOH8 reduces HIF-2α abundance not defined
    • Whether this is transcription-independent unclear
  6. 2019 Medium

    Showed ATOH8 expression is silenced epigenetically by EZH2 via H3K27me3 and DNA methylation, establishing an upstream repression mechanism controlling ATOH8 levels in cancer.

    Evidence ChIP and bisulfite sequencing downstream of a Lnc-PDZD7/miR-101/EZH2 axis in HCC

    PMID:30786928

    Open questions at the time
    • Single lab
    • Direct EZH2 recruitment to ATOH8 promoter not shown in this study
  7. 2019 Medium

    Extended ATOH8's developmental role to endochondral bone, showing it regulates chondrocyte proliferation and hypertrophy relative to Ihh signaling.

    Evidence Conditional/germline knockout mice with Purmorphamine Ihh-pathway epistasis

    PMID:31449527

    Open questions at the time
    • Direct targets in chondrocytes not identified
    • Whether Ihh is a direct ATOH8 target unresolved
  8. 2020 High

    Defined ATOH8 as a SMAD1-coupled brake on osteoclastogenesis via a Runx2 complex that lowers the Rankl/Opg ratio.

    Evidence Co-IP of Atoh8-Runx2, knockout mice, osteoclastogenesis assays, and Runx2 knockdown epistasis

    PMID:32923015

    Open questions at the time
    • Whether ATOH8 binds DNA or only sequesters Runx2 not distinguished
    • Genomic targets of the complex not mapped
  9. 2020 Medium

    Revealed a context where ATOH8 is pro-tumorigenic—a VEGFR2/AKT axis upregulates ATOH8 to activate HK2 and glycolysis, supporting circulating tumor cell survival.

    Evidence Shear-stress system, glycolysis/anoikis assays, and pathway inhibitor experiments

    PMID:32000836

    Open questions at the time
    • Direct binding to HK2 promoter not shown
    • Single lab
    • Reconciliation with ATOH8's tumor-suppressive contexts unaddressed
  10. 2021 Medium

    Identified additional epigenetic and isoform-level control: lncRNA CIR recruits EZH2 to silence ATOH8 in MSCs, and an ATOH8-V1 isoform activates RhoC to drive metastasis.

    Evidence RNA-IP/biotin pull-down and ChIP in MSCs; ChIP and reporter assays for ATOH8-V1/RhoC

    PMID:33049034 PMID:33546582

    Open questions at the time
    • Functional distinction between ATOH8 isoforms incompletely mapped
    • Single lab for each
  11. 2021 Medium

    Showed ATOH8 restrains differentiation programs in immune and epithelial contexts, limiting intestinal M cell maturation under PRC2 control.

    Evidence Atoh8 knockout mice and RankL-treated intestinal organoids

    PMID:34502262

    Open questions at the time
    • Direct ATOH8 targets in M cell program not identified
    • Single lab
  12. 2022 Medium

    Generalized ATOH8's role to a genome-wide enhancer-binding restraint on cellular plasticity within a c-Myc/Atoh8/Sfrp1 axis, beyond any single cell identity.

    Evidence Single-cell multiomics with enhancer-binding analysis during reprogramming and transformation

    PMID:36075976

    Open questions at the time
    • Precise enhancer recognition code unresolved
    • How c-Myc and Atoh8 antagonize at shared loci not defined
  13. 2023 High

    Established the SMAD3-ATOH8 repressive complex as the effector of oncogene-induced senescence and a tumor-suppressive brake on Ras-driven lung cancer with pharmacological relevance.

    Evidence Co-IP, ChIP-seq/reporter assays, knockout mice with oncogenic Ras, and SMAD3 inhibitor treatment

    PMID:36626550

    Open questions at the time
    • SMAD2/SMAD4 exclusion mechanism not structurally explained
    • Full cell-cycle target set not enumerated
  14. 2023 Medium

    Positioned ATOH8 as an upstream BMP2/cAMP-induced nuclear regulator of the WNT/FZD-FOXO1 decidualization program in endometrial stromal cells.

    Evidence siRNA/overexpression with BMP2/ALK inhibitors, cAMP analogue, and nuclear-localization imaging

    PMID:38060684

    Open questions at the time
    • Whether FZD4/FOXO1 are direct targets not shown
    • Single lab
  15. 2024 Medium

    Added post-transcriptional control by showing FXR1 binds the ATOH8 3'UTR to promote its mRNA degradation in esophageal cancer.

    Evidence 3'UTR interaction and mRNA stability assays with FXR1 perturbation

    PMID:39511680

    Open questions at the time
    • Whether degradation requires additional decay machinery unclear
    • Single lab
  16. 2025 Medium

    Defined a TCF3-ATOH8 repressive complex at SCD that controls ferroptosis sensitivity, and reaffirmed EZH2-driven silencing of ATOH8 in this axis.

    Evidence Co-IP, SCD reporter assays, ChIP for EZH2/H3K27me3, and ferroptosis assays in vitro and in vivo

    PMID:40133667

    Open questions at the time
    • Relative contribution of TCF3 versus E47 as ATOH8 partners not compared
    • Single lab
  17. 2025 Medium

    Identified calcineurin (PPP3CB) as a regulator of ATOH8 nuclear translocation enabling Sp1 repression and metastasis suppression in pancreatic cancer.

    Evidence Co-IP validated by mass spectrometry, ChIP-seq, reporter assays, nuclear-localization imaging, and xenografts

    PMID:40222712

    Open questions at the time
    • Whether PPP3CB dephosphorylates ATOH8 directly not shown
    • Single lab
  18. 2025 Medium

    Connected ATOH8 loss to renal disease through TGF-β/SMAD pathway derepression (podocytes/FSGS) and uncovered WTAP-dependent m6A as another layer of ATOH8 mRNA control (mesangial cells/diabetic nephropathy).

    Evidence shRNA knockdown with SMAD reporter/imaging plus adriamycin nephropathy mice; MeRIP-Seq with WTAP knockdown and db/db model

    PMID:40399698 PMID:41545031

    Open questions at the time
    • Direct ATOH8 targets restraining TGF-β output not mapped
    • m6A reader mediating Atoh8 destabilization not identified
    • Single lab each
  19. 2025 Medium

    Expanded ATOH8 function beyond transcriptional repression by showing direct binding to autophagosome-assembly genes and a role in sustaining autophagic flux, and confirmed a role in extravillous trophoblast differentiation.

    Evidence Cut&Tag and autophagy-marker westerns in myoblasts/ESCs; siRNA/RNA-seq and invasion assays in human trophoblast stem cells

    PMID:41188410 PMID:41440013

    Open questions at the time
    • Whether autophagy genes are activated or repressed by ATOH8 not fully clarified
    • Direct EVT target genes not defined
    • Single lab each

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what determines ATOH8's switch between activator and repressor at a given locus, and how its many cofactor partnerships (E47, SMAD3, SMAD1/5, Runx2, TCF3, HIF-2α) are selected in a tissue- and signal-specific manner.
  • No structural model of ATOH8 cofactor complexes
  • No unified genome-wide binding map across cell types
  • Functional distinction among ATOH8 isoforms incompletely characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6 GO:0098772 molecular function regulator activity 5
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-9612973 Autophagy 1
Partners
CYP3A5E47FXR1HIF-2APPP3CBRUNX2SMAD3TCF3

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 ATOH8 activates HAMP (hepcidin) transcription by directly binding E-box regions within the HAMP promoter (shown by ChIP assay), and also indirectly through BMP signaling by increasing phosphorylated SMAD1/5/8 levels; mutation of E-box or SMAD response elements in the HAMP promoter significantly reduced ATOH8-mediated activation. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, site-directed mutagenesis of promoter elements, western blot for pSMAD1/5/8 British journal of haematology High 24236640
2013 ATOH8 lacks a canonical transactivation domain and possesses intrinsic repressor activity dependent on a conserved Proline-rich domain. ATOH8 binds the ubiquitous E protein E47 and inhibits E47/E47 and Neurogenin3/E47 dimer transcriptional activities, thereby blocking induction of a subset of proendocrine gene targets. Reporter assays, domain deletion/mutagenesis, co-immunoprecipitation, global gene expression profiling in pancreatic mPAC cells Biochimica et biophysica acta High 23938248
2019 ATOH8 is a direct transcriptional target of the BMP-SMAD1/5 axis in endothelial cells; ATOH8 induction by BMP is independent of Notch signaling. ATOH8 protein interacts with HIF-2α and decreases its abundance, leading to reduced transcription of HIF-2α target genes under hypoxia. Atoh8-deficient mice develop a pulmonary arterial hypertension-like phenotype (increased pulmonary arterial pressure, right ventricular hypertrophy). Co-immunoprecipitation (ATOH8–HIF-2α interaction), reporter assays, genetic knockout mice, in vivo hemodynamic measurements, zebrafish studies Science signaling High 31719172
2020 BMP-SMAD1 signaling directly upregulates Atoh8 in osteoblasts. Atoh8 forms a protein complex with Runx2 to inhibit Runx2 transcriptional activity, thereby reducing the Rankl/Opg expression ratio in osteoblasts and suppressing osteoclastogenesis. Atoh8-null marrow stroma cells were more potent than wild-type cells in inducing osteoclastogenesis. Co-immunoprecipitation (Atoh8–Runx2 complex), gene expression analysis, Atoh8 global knockout mice, marrow stromal cell osteoclastogenesis assays, Runx2 knockdown epistasis Bone research High 32923015
2023 ATOH8 binds SMAD3 (but not SMAD2 or SMAD4) to form a transcriptional repressive complex that directly represses cell cycle-promoting genes, causing oncogene-induced senescence in lung epithelial cells downstream of TGF-β1/SMAD3 activation. Depleting Atoh8 accelerates oncogenic Ras-driven lung tumorigenesis in vivo, and lung cancers driven by mutant Ras plus Atoh8 loss are sensitive to a specific SMAD3 inhibitor. Co-immunoprecipitation (ATOH8–SMAD3), ChIP-seq/reporter assays for target gene repression, Atoh8 knockout mice with oncogenic Ras, SMAD3 inhibitor treatment Proceedings of the National Academy of Sciences of the United States of America High 36626550
2014 ATOH8 (Hath6) acts as a shear-stress-responsive transcription factor in endothelial cells. Overexpression of Hath6 (mimicking shear stress) increases endothelial differentiation markers (CD45−CD31+KDR+ population, tubular structure formation) and endothelial gene expression. The eNOS gene is a direct transcriptional target of Hath6, demonstrated by reporter assay; inhibition of eNOS diminishes hESC-to-endothelial cell differentiation. Gain- and loss-of-function in hESC-EC induction system, luciferase reporter assay for eNOS promoter, western blot, in situ hybridization in zebrafish and mouse embryos Journal of cell science Medium 24463812
2015 ATOH8 represses transcription of stem-cell-associated genes OCT4, NANOG, and CD133 in hepatocellular carcinoma cells, as demonstrated by mobility shift and luciferase reporter assays. Transgenic ATOH8 expression reduces CD133+ cell populations, tumor formation, and invasion, while ATOH8 knockdown causes CD133-negative cells to acquire stem-cell properties. Electrophoretic mobility shift assay (EMSA), luciferase reporter assay, lentiviral overexpression and siRNA knockdown, xenograft tumor assays, flow cytometry Gastroenterology High 26099525
2020 In response to laminar shear stress, VEGF is released by circulating colorectal cancer cells, activating a VEGFR2/AKT signaling axis that upregulates ATOH8 expression. ATOH8 then transcriptionally activates HK2, promoting glycolysis and intravascular survival of tumor cells. Western blotting, quantitative PCR, immunofluorescence, glycolysis assay, anoikis assay, cyclic laminar shear stress system, pathway inhibitor experiments Journal of experimental & clinical cancer research : CR Medium 32000836
2019 EZH2 represses ATOH8 expression in HCC cells via H3K27 trimethylation and DNA methylation of the ATOH8 promoter, as demonstrated by chromatin immunoprecipitation and bisulfite genomic sequencing. This mechanism operates downstream of the Lnc-PDZD7/miR-101/EZH2 axis. Chromatin immunoprecipitation (ChIP), bisulfite genomic sequencing, dual-luciferase reporter assay, western blot Journal of experimental & clinical cancer research : CR Medium 30786928
2021 LncRNA CIR binds EZH2 (shown by RNA immunoprecipitation and biotin pull-down) and recruits it to the ATOH8 promoter, resulting in EZH2-mediated H3K27me3 and methylation-based repression of ATOH8 in mesenchymal stem cells. Loss of lncRNA CIR or overexpression of ATOH8 promotes chondrogenic differentiation; inhibition of ATOH8 reverses effects of lncRNA CIR knockdown. RNA immunoprecipitation, biotin pull-down, ChIP, western blot, qRT-PCR, gain/loss-of-function in hUC-MSCs Molecular medicine (Cambridge, Mass.) Medium 33546582
2016 EBV-encoded LMP1 inhibits ATOH8 expression in nasopharyngeal carcinoma cells by epigenetically reducing activating H3K4me3 and increasing repressive H3K27me3 occupancy on the ATOH8 promoter, as shown by ChIP assay. ATOH8 restoration reverses the LMP1-induced malignant phenotype. ChIP assay for H3K4me3 and H3K27me3, gain/loss-of-function assays, western blot, real-time PCR Oncotarget Medium 27049918
2021 A novel isoform, ATOH8-V1, directly binds the RhoC promoter and transcriptionally activates RhoC expression, thereby enhancing metastasis of breast cancer cells. ChIP assay, luciferase reporter assay, overexpression and silencing of ATOH8-V1, metastasis assays Journal of molecular cell biology Medium 33049034
2019 Atoh8 regulates chondrocyte proliferation and hypertrophic differentiation in endochondral bones. Atoh8 deletion (chondrocyte-specific and germline) leads to reduced zones of proliferating and hypertrophic chondrocytes and shorter bones. Atoh8 acts on the onset of hypertrophy upstream of Ihh (likely modulating Ihh expression), while regulating chondrocyte proliferation in parallel or downstream of Ihh signaling (demonstrated by Purmorphamine activation of Ihh pathway). Conditional and germline Atoh8 knockout mice (Col2a1-Cre; Prx1-Cre), histological analysis, Purmorphamine (Ihh agonist) epistasis experiment, molecular marker analysis PloS one Medium 31449527
2022 Atoh8 restrains cellular plasticity (reprogramming and oncogenic transformation) independently of cellular identity by binding a specific enhancer network, as part of a c-Myc/Atoh8/Sfrp1 regulatory axis identified by multiomics characterization at single-cell resolution. Single-cell multiomics (scRNA-seq, epigenomics), chromatin binding analysis of enhancer networks, genetic perturbation during reprogramming and transformation Nature cell biology Medium 36075976
2025 ATOH8 suppresses SCD (stearoyl-CoA desaturase) transcription, sensitizing tumor cells to ferroptosis. TCF3 acts as a co-factor with ATOH8, forming a TCF3-ATOH8 transcriptional repressive complex at the SCD locus. EZH2 epigenetically suppresses ATOH8 expression via DNA methylation of the ATOH8 promoter and H3K27me3 elevation. Overexpression/deletion of ATOH8 in tumor cells, reporter assays for SCD transcription, co-immunoprecipitation of TCF3-ATOH8 complex, ChIP for EZH2/H3K27me3 at ATOH8 promoter, ferroptosis sensitivity assays in vitro and in vivo Cell death and differentiation Medium 40133667
2025 PPP3CB (calcineurin) physically interacts with ATOH8 (shown by co-immunoprecipitation confirmed by mass spectrometry) and promotes ATOH8 nuclear translocation in pancreatic cancer cells. Nuclear ATOH8 binds the Sp1 promoter (shown by ChIP-seq and luciferase assay) and transcriptionally inhibits Sp1, suppressing pancreatic cancer metastasis. Liquid chromatography-tandem mass spectrometry, co-immunoprecipitation, ChIP-seq, luciferase reporter assay, immunofluorescence/confocal microscopy for nuclear translocation, xenograft mouse models Life sciences Medium 40222712
2024 FXR1 (RNA-binding protein) binds the 3'UTR of ATOH8 mRNA and promotes its degradation, negatively regulating ATOH8 at the post-transcriptional level in esophageal cancer cells. Direct 3'UTR interaction assay, mRNA stability assay, FXR1 knockdown/overexpression experiments, in vitro and in vivo functional assays Biology direct Medium 39511680
2025 WTAP methyltransferase promotes m6A modification of Atoh8 mRNA, reducing its stability and expression in mesangial cells. Reduced Atoh8 promotes mesangial cell proliferation and fibrosis in diabetic nephropathy; overexpression of Atoh8 restrained these processes. MeRIP-Seq combined with RNA-Seq, WTAP knockdown, Atoh8 overexpression in mouse mesangial cells, db/db mouse model Cell biochemistry and biophysics Medium 40399698
2025 Loss of ATOH8 in podocytes activates TGF-β signaling: ATOH8-knockdown podocytes show SMAD2/3 nuclear translocation, increased SMAD transcriptional activity (luciferase assay), upregulated TGFB1 mRNA, and increased extracellular matrix gene expression even without exogenous TGF-β. In vivo, Atoh8-deficient mice develop more severe glomerulosclerosis in an adriamycin-induced FSGS model. shRNA knockdown, RNA sequencing, SMAD2/3 localization imaging, SMAD luciferase reporter assay, Atoh8 knockout mouse + adriamycin nephropathy model American journal of physiology. Renal physiology Medium 41545031
2023 BMP2 (via ALK2/3 receptor) and cAMP signaling upregulate ATOH8 expression during human endometrial stromal fibroblast (ESF) decidualization. ATOH8 protein localizes predominantly to the nucleus in decidualizing cells. ATOH8 silencing reduces FZD4 and FOXO1 expression and downstream FOXO1 targets, placing ATOH8 as a major upstream regulator of the WNT/FZD-FOXO1 pathway in decidualization. siRNA knockdown and overexpression of ATOH8, BMP2/ALK2/3 inhibitor treatment, cAMP analogue treatment, immunofluorescence for nuclear localization, qRT-PCR and western blot Endocrinology Medium 38060684
2021 PRC2-regulated Atoh8 restrains intestinal M cell differentiation: Atoh8 null mice showed a significant increase in mature M cells (Gp2+), M cell-associated markers (Spi-B, Sox8), and increased transcytosis of luminal antigens in Peyer's patches. Atoh8 knockout mice, RankL-treated intestinal organoids, immunofluorescence, in vitro organoid analysis International journal of molecular sciences Medium 34502262
2025 Loss of Atoh8 impairs macroautophagy: Atoh8-null primary myoblasts and mouse embryonic stem cells show differential LC3B-II expression, TFEB levels, and accumulation of p62 (autophagy cargo receptor). Cut&Tag sequencing in Atoh8-overexpressing C2C12 cells revealed Atoh8 binding to multiple genes involved in autophagosome assembly. Atoh8 overexpression increases autophagic flux while its loss disrupts it. Western blot for autophagy markers (LC3B-II, p62, TFEB), mass spectrometry proteomics, Cut&Tag sequencing for chromatin binding in Atoh8-overexpressing cells, Atoh8 knockout myoblasts and ESCs Cells Medium 41440013
2010 Atoh8 is required for retinal lamination and skeletal muscle fiber differentiation in zebrafish. Morpholino-mediated knockdown results in reduced eye size with disorganization of retinal lamination and disrupted arrangement of paraxial cells and differentiated muscle fibers during somite morphogenesis. Morpholino knockdown in zebrafish, whole-mount in situ hybridization, histological analysis of retina and somites PloS one Low 20532172
2025 ATOH8 is required for extravillous trophoblast (EVT) differentiation from human trophoblast stem cells. ATOH8 knockdown during EVT differentiation causes morphological abnormalities, impaired EVT marker expression, sustained TSC marker expression, and abolished invasive capacity, while disrupting extracellular matrix organization and PI3K-AKT signaling pathways. ATOH8 functions within a cooperative transcriptional network of EVT regulators, reciprocally regulating their expression. ATOH8 siRNA knockdown and overexpression in human TSCs, transcriptomic profiling (RNA-seq), invasion assays, marker expression analysis Scientific reports Medium 41188410
2019 GDF5 promotes neuronal differentiation of retinal stem cells through activation of Smad signaling, and this effect is mediated by Atoh8; Atoh8 modulates the GDF5-induced neurogenesis and neurite outgrowth. Retinal stem cell differentiation assay, Atoh8 gain/loss-of-function, Smad signaling pathway analysis Journal of cellular physiology Low 31066042
2020 CYP3A5 interacts with ATOH8 by co-immunoprecipitation in lung adenocarcinoma cells, and this interaction mediates inactivation of the Smad1 phosphorylation pathway, suppressing metastasis. Co-immunoprecipitation, high-throughput phosphorylation chip, western blot, in vitro migration/invasion assays, in vivo metastasis model American journal of cancer research Low 33163265

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Loss of ATOH8 Increases Stem Cell Features of Hepatocellular Carcinoma Cells. Gastroenterology 53 26099525
2020 Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation. Journal of experimental & clinical cancer research : CR 52 32000836
2019 Lnc-PDZD7 contributes to stemness properties and chemosensitivity in hepatocellular carcinoma through EZH2-mediated ATOH8 transcriptional repression. Journal of experimental & clinical cancer research : CR 44 30786928
2020 BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts. Bone research 38 32923015
2014 The role of Hath6, a newly identified shear-stress-responsive transcription factor, in endothelial cell differentiation and function. Journal of cell science 36 24463812
2021 Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2. Molecular medicine (Cambridge, Mass.) 34 33546582
2010 Atoh8, a bHLH transcription factor, is required for the development of retina and skeletal muscle in zebrafish. PloS one 33 20532172
2019 The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension. Science signaling 28 31719172
2022 Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity. Nature cell biology 26 36075976
2011 Diversification and molecular evolution of ATOH8, a gene encoding a bHLH transcription factor. PloS one 25 21857980
2016 Downregulation of ATOH8 induced by EBV-encoded LMP1 contributes to the malignant phenotype of nasopharyngeal carcinoma. Oncotarget 24 27049918
2013 The transcription factor ATOH8 is regulated by erythropoietic activity and regulates HAMP transcription and cellular pSMAD1,5,8 levels. British journal of haematology 23 24236640
2023 ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation. Proceedings of the National Academy of Sciences of the United States of America 21 36626550
2014 ATOH8: a novel marker in human muscle fiber regeneration. Histochemistry and cell biology 21 25514850
2022 Atoh8 in Development and Disease. Biology 20 35053134
2013 Characterization of the transcriptional activity of the basic helix-loop-helix (bHLH) transcription factor Atoh8. Biochimica et biophysica acta 19 23938248
2017 Zebrafish atoh8 mutants do not recapitulate morpholino phenotypes. PloS one 18 28182631
2021 A novel isoform of ATOH8 promotes the metastasis of breast cancer by regulating RhoC. Journal of molecular cell biology 16 33049034
2019 Atoh8 acts as a regulator of chondrocyte proliferation and differentiation in endochondral bones. PloS one 14 31449527
2024 FXR1 associates with and degrades PDZK1IP1 and ATOH8 mRNAs and promotes esophageal cancer progression. Biology direct 13 39511680
2019 Growth/differentiation 5 promotes the differentiation of retinal stem cells into neurons via Atoh8. Journal of cellular physiology 12 31066042
2016 Generation of a Conditional Allele of the Transcription Factor Atonal Homolog 8 (Atoh8). PloS one 11 26752640
2023 ATOH8 Expression Is Regulated by BMP2 and Plays a Key Role in Human Endometrial Stromal Cell Decidualization. Endocrinology 9 38060684
2020 ATOH8 overexpression inhibits the tumor progression and monocyte chemotaxis in hepatocellular carcinoma. International journal of clinical and experimental pathology 9 33165366
2021 PRC2 Regulated Atoh8 Is a Regulator of Intestinal Microfold Cell (M Cell) Differentiation. International journal of molecular sciences 8 34502262
2020 CYP3A5 suppresses metastasis of lung adenocarcinoma through ATOH8/Smad1 axis. American journal of cancer research 7 33163265
2023 ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes. Molecular medicine reports 6 37232357
2021 atoh8 expression pattern in early zebrafish embryonic development. Histochemistry and cell biology 6 34120256
2021 Targeted deletion of Atoh8 results in severe hearing loss in mice. Genesis (New York, N.Y. : 2000) 6 34402594
2025 ATOH8 confers the vulnerability of tumor cells to ferroptosis by repressing SCD expression. Cell death and differentiation 2 40133667
2024 The Effects of Atoh8 on Postnatal Murine Neurogenesis. Cells, tissues, organs 2 39191233
2022 Bcl11b and Atoh8 Coordinate Cellular Plasticity for Reprogramming and Transformation. Cellular reprogramming 2 36409720
2025 PPP3CB inhibits pancreatic cancer progression by promoting ATOH8 translocation and transcriptionally regulating Sp1. Life sciences 1 40222712
2026 Loss of transcription factor ATOH8 activates TGF-β signaling and exacerbates glomerulosclerosis in podocytes. American journal of physiology. Renal physiology 0 41545031
2025 Loss of Atoh8 Affects Neurocranial and Axial Skeleton Development in Zebrafish. Frontiers in bioscience (Landmark edition) 0 40152384
2025 Atoh8 expression inhibition promoted osteogenic differentiation of ADSCs and inhibited cell proliferation in vitro and rat bone defect models. Adipocyte 0 40356232
2025 WTAP-induced m6A Methylation of Atoh8 Promotes Cell Proliferation and Fibrosis in Diabetic Nephropathy. Cell biochemistry and biophysics 0 40399698
2025 ATOH8 is crucial for the differentiation of human trophoblast stem cells into extravillous trophoblasts. Scientific reports 0 41188410
2025 Loss of Atoh8 Impairs Macroautophagy. Cells 0 41440013
2024 LncRNA RP11-301G19.1 is required for the maintenance of vascular smooth muscle cell contractile phenotype via sponging miR-17-5P/ATOH8 axis. IUBMB life 0 38651683

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