Affinage

POU4F3

POU domain, class 4, transcription factor 3 · UniProt Q15319

Length
338 aa
Mass
37.1 kDa
Annotated
2026-04-28
70 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POU4F3 is a POU-domain transcription factor essential for the differentiation, maturation, and lifelong survival of mechanosensory hair cells in the inner ear and retinal ganglion cells. It operates downstream of ATOH1 in a feed-forward circuit: ATOH1 induces POU4F3 expression, and POU4F3 then acts as a pioneer factor to open closed chromatin at ATOH1 target enhancers, enabling terminal differentiation of hair cells and Merkel cells (PMID:34266958, PMID:22985730). POU4F3 directly activates transcription of downstream targets including Gfi1, Lhx3, Nr2f2, Caprin-1, Rbm24, PLSCR5, BDNF, and NT-3 through its POU-specific and POU-homeodomain DNA-binding domains, requiring intact bipartite nuclear localization signals for nuclear import (PMID:15254021, PMID:17331196, PMID:25372459, PMID:38483314, PMID:14585957). Dominant mutations in POU4F3 that impair DNA binding, transcriptional activation, or nuclear localization cause DFNA15 autosomal dominant progressive hearing loss, and base editing to restore POU4F3 function achieves near-complete hearing rescue in a mouse model (PMID:9506947, PMID:18228599, PMID:40968144).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Establishing POU4F3 as a survival factor for inner ear hair cells resolved the question of which transcription factor is required for mechanosensory cell maintenance in the cochlea and vestibule.

    Evidence Targeted Brn-3c knockout mice showed complete hair cell loss and secondary ganglion neuron degeneration

    PMID:9256502

    Open questions at the time
    • Upstream regulators of POU4F3 expression unknown
    • Whether POU4F3 is needed for initial hair cell specification versus maintenance was unresolved
    • Direct transcriptional targets unidentified
  2. 1998 High

    Demonstrating that POU4F3-null hair cells initiate differentiation but fail to mature and undergo apoptosis separated its role in survival/maturation from progenitor specification, and identification of the first human DFNA15 mutation linked POU4F3 to hereditary deafness.

    Evidence Brn-3c knockout mice showed initial hair cell marker expression but absent stereocilia and apoptotic degeneration; an 8-bp POU homeodomain deletion cosegregated with progressive hearing loss in a human kindred

    PMID:9506947 PMID:9579678 PMID:9735355

    Open questions at the time
    • Mechanism of apoptosis induction in POU4F3-null cells unknown
    • Functional consequence of the human mutation not directly tested
  3. 2003 High

    Functional dissection of the DFNA15 mutation and identification of two nuclear localization signals revealed that DNA-binding loss, impaired nuclear import, and altered protein stability collectively underlie dominant-negative pathogenesis.

    Evidence Cell-based transfection assays measuring DNA binding, reporter activation, subcellular localization, and protein half-life of wild-type versus mutant POU4F3

    PMID:14585957

    Open questions at the time
    • Whether haploinsufficiency or dominant-negative mechanism predominates in vivo was unresolved
    • Structural basis of NLS function not determined
  4. 2004 High

    Identification of Gfi1 and neurotrophins BDNF/NT-3 as direct POU4F3 targets established a downstream gene regulatory network maintaining hair cell identity and trophic support for innervating neurons.

    Evidence Microarray profiling of Pou4f3-mutant versus wild-type ears combined with EMSA/footprinting on BDNF and NT-3 promoters

    PMID:15254021 PMID:15465029

    Open questions at the time
    • Full set of direct targets unknown
    • Whether Gfi1 alone mediates outer hair cell survival not tested
  5. 2007 High

    Discovery of Lhx3 as a POU4F3-dependent target with differential auditory versus vestibular regulation expanded the target network and revealed context-dependent transcriptional output.

    Evidence Microarray and RT-PCR in Pou4f3-mutant mouse inner ears with in situ hybridization validation

    PMID:17331196

    Open questions at the time
    • Direct binding to Lhx3 regulatory elements not demonstrated
    • Functional consequence of Lhx3 loss in hair cells unknown at the time
  6. 2008 High

    Two additional DFNA15 missense mutations in the POU-specific and POU-homeodomain each caused cytoplasmic mislocalization and transcriptional impairment, generalizing the mechanism that diverse POU domain disruptions converge on impaired nuclear function to cause deafness.

    Evidence Immunofluorescence, reporter gene assays, and structural modeling of L289F and L223P variants

    PMID:18228599

    Open questions at the time
    • Whether partial nuclear localization retains residual transcriptional activity in vivo unknown
    • Genotype-phenotype severity correlation not established
  7. 2012 Medium

    Identification of ATOH1, TCF3, and GATA3 as cooperative upstream activators of Pou4f3 transcription through a conserved 5′ enhancer region placed POU4F3 into a defined upstream regulatory hierarchy.

    Evidence Electroporation of cochlear explants with transcription factor combinations and Pou4f3/GFP transgenic reporter readout

    PMID:22985730

    Open questions at the time
    • Whether these factors bind simultaneously or sequentially not resolved
    • Chromatin state at the Pou4f3 enhancer not characterized
  8. 2014 High

    Demonstration that Nr2f2 is a direct POU4F3 target via EMSA and mutagenesis of binding sites expanded the network of hair cell identity genes under POU4F3 control.

    Evidence EMSA showing POU4F3 binding to Nr2f2 5′ flanking sites, mutant reporter assays

    PMID:25372459

    Open questions at the time
    • In vivo validation of Nr2f2 dependence on POU4F3 not shown at the time
    • Nr2f2 function in hair cells unknown
  9. 2017 Medium

    Showing that POU4F3 alone or combined with ATOH1 could convert adult supporting cells into hair cells in vivo established POU4F3 as a potent reprogramming factor and potential therapeutic tool for hearing restoration.

    Evidence In vivo ectopic expression with lineage tracing in adult mouse cochlea

    PMID:28402854

    Open questions at the time
    • Functional maturity of converted hair cells not assessed electrophysiologically
    • Long-term stability of reprogrammed cells unknown
  10. 2021 High

    ATAC-seq and ChIP-seq revealed POU4F3 acts as a pioneer transcription factor downstream of ATOH1, opening closed chromatin at ATOH1 target enhancers — this resolved the mechanistic basis of the ATOH1–POU4F3 feed-forward loop as an epigenetic gating mechanism.

    Evidence ATAC-seq and ChIP-seq in conditional POU4F3 knockout hair cells and Merkel cells combined with in vivo reporter assays

    PMID:34266958

    Open questions at the time
    • Biochemical mechanism of pioneer activity (cofactors, chromatin remodelers recruited) not identified
    • Whether pioneer function depends on specific POU domain contacts unknown
  11. 2022 High

    Combined single-cell transcriptomics and ATAC-seq showed that age-dependent epigenetic barriers to hair cell reprogramming can be overcome by the ATOH1/GFI1/POU4F3 transcription factor combination, placing POU4F3 in a defined minimal set for therapeutic regeneration.

    Evidence scRNA-seq with matched ATAC-seq and inducible Cre mouse models across postnatal ages

    PMID:36445327

    Open questions at the time
    • Relative contribution of each factor to chromatin remodeling not dissected
    • Whether this combination suffices in the human cochlea unknown
  12. 2023 High

    Identification of Rbm24 as a direct POU4F3 target through in vivo enhancer binding, with genetic epistasis showing it lies downstream of POU4F3 but not Gfi1, refined the branching architecture of the hair cell gene regulatory network.

    Evidence In vivo transgenic reporter assays for three Rbm24 enhancers, conditional knockout epistasis with Pou4f3 and Gfi1

    PMID:38483314

    Open questions at the time
    • Rbm24 alone insufficient to rescue POU4F3-null hair cells — additional essential targets remain unidentified
    • RNA targets of Rbm24 in hair cells unknown
  13. 2024 High

    Inducible postnatal deletion of Pou4f3 at multiple ages demonstrated a continuous, lifelong requirement for POU4F3 in hair cell survival, with faster degeneration in immature cells, ruling out a development-only role.

    Evidence Inducible CreER-loxP deletion at P0, P7, P14, and adult, with ABR and hair cell quantification

    PMID:38566840

    Open questions at the time
    • Molecular basis of age-dependent degeneration kinetics unexplained
    • Whether POU4F3 maintains the same target gene repertoire in mature versus developing hair cells unknown
  14. 2025 High

    Base editing of a POU4F3 nonsense allele in neonatal mice achieved near-complete hearing rescue, providing proof-of-concept that gene correction of DFNA15 mutations is therapeutically viable.

    Evidence AAV-delivered adenine base editor (SchABE8e via Anc80L65) in Pou4f3Q113* mice with ABR functional readout

    PMID:40968144

    Open questions at the time
    • Long-term durability of base editing correction unknown
    • Applicability to missense DFNA15 alleles not tested
    • Delivery efficiency to adult hair cells not demonstrated
  15. 2025 Medium

    POU4F3 was shown to be specifically required for type I but not type II vestibular hair cell subtype differentiation, and PLSCR5 was identified as a downstream target essential for stereocilia homeostasis.

    Evidence Two independent Pou4f3 mouse models with vestibular analysis; Plscr5 knockout mice with ABR/DPOAE and phosphatidylserine externalization assays

    PMID:40068798 PMID:40850952

    Open questions at the time
    • Mechanism by which POU4F3 differentially controls type I versus type II HC fate unknown
    • How PLSCR5-mediated phosphatidylserine externalization maintains stereocilia integrity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical mechanism of POU4F3's pioneer factor activity — including which chromatin remodeling complexes it recruits and how it achieves locus selectivity — remains uncharacterized.
  • No structural model of POU4F3 bound to nucleosomal DNA
  • Cofactors mediating chromatin opening not identified
  • Complete direct target gene set not defined genome-wide by CUT&RUN or equivalent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 5 R-HSA-112316 Neuronal System 4 R-HSA-4839726 Chromatin organization 2
Partners
ATOH1CAPRIN1GATA3GFI1LHX3NR2F2RBM24

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Targeted deletion of Brn-3c (POU4F3) in mice results in complete loss of auditory and vestibular hair cells during late embryonic and early postnatal period, with secondary loss of spiral and vestibular ganglion neurons, establishing POU4F3 as essential for hair cell survival in the inner ear. Targeted gene deletion (knockout mouse), histology, behavioral testing Proceedings of the National Academy of Sciences of the United States of America High 9256502
1998 POU4F3 is required for maturation, survival, and migration of hair cells, but not for proliferation or commitment of hair cell progenitors; in Brn-3c-/- mice, hair cells are generated and undergo initial differentiation (expressing myosins VI and VIIa, calretinin, parvalbumin) but fail to form stereociliary bundles and degenerate by apoptosis. Knockout mouse analysis, immunohistochemistry, morphological analysis, in situ hybridization Development (Cambridge, England) High 9735355
1998 An 8-base pair deletion in the POU homeodomain of human POU4F3 causes DFNA15 progressive hearing loss; the truncated protein presumably impairs high-affinity DNA binding in a dominant negative fashion. Linkage analysis, sequence analysis, genetic mapping Science (New York, N.Y.) Medium 9506947
1998 POU4F3 (Brn-3c) contains an N-terminal activation domain with neuronal cell-specific transcriptional activity; this domain activates gene promoters only in neuronal cells and not in other cell types. Transient transfection assays in neuronal and non-neuronal cell lines, domain deletion constructs Neuroreport Medium 9579678
2002 Brn-3c (POU4F3) controls ipsilateral retinal ganglion cell axon production and promotes axon outgrowth; forced expression of Brn-3c in Brn-3b-/- retinal explants restored neurite outgrowth, demonstrating Brn-3c can promote axon outgrowth in the absence of Brn-3b. Double knockout mouse generation, retinal explant culture, forced expression rescue experiment, optic chiasm analysis Development (Cambridge, England) High 11807038
2003 The DFNA15 mutation in POU4F3 causes loss of most transcriptional activity, loss of DNA-binding ability, altered subcellular localization (protein found in both nucleus and cytoplasm instead of exclusively nuclear), and increased protein half-life compared to wild-type; two nuclear localization signals were identified, both essential for proper nuclear entry. Cell culture transfection, reporter assays, subcellular localization studies, DNA-binding assays, protein stability assays Molecular and cellular biology High 14585957
2004 Gfi1 is a direct downstream target gene regulated by POU4F3 in vivo in hair cells; Pou4f3 deficiency leads to statistically significant reduction in Gfi1 expression, and Gfi1 expression dynamics closely follow Pou4f3 expression, with outer hair cell degeneration in Pou4f3 mutants largely resulting from loss of Gfi1 expression. Oligonucleotide microarray expression profiling, semi-quantitative RT-PCR, in situ hybridization, immunohistochemistry, scanning electron microscopy Human molecular genetics High 15254021
2004 POU4F3 (Brn-3c) directly binds specific elements within the BDNF and NT-3 promoters in vitro and activates both promoters in inner ear sensory epithelial cell lines; BDNF expression is reduced in Brn-3c mutant mouse inner ear during embryogenesis. Transient transfection assays, in vitro DNA-binding analysis (footprinting/EMSA), in vivo expression analysis in mutant mice Biochemical and biophysical research communications High 15465029
2005 Brn-3c contains an independent N-terminal activation domain sufficient to activate gene transcription in organ-of-Corti-derived cell lines, as shown by GAL4 domain-swap experiments. GAL4 fusion domain-swap assay, co-transfection in OC-1 and OC-2 cell lines Brain research. Molecular brain research Medium 16226339
2007 Lhx3, a LIM domain transcription factor expressed in all inner ear hair cells, is a downstream target gene regulated by POU4F3 in vivo; its mRNA level is greatly reduced in Pou4f3 mutant mice, with differential regulation in auditory versus vestibular hair cells. Oligonucleotide microarray, RT-PCR validation, in situ hybridization, mutant mouse analysis The European journal of neuroscience High 17331196
2007 A common polymorphic poly-G repeat at position -3432 of the Brn-3c/POU4F3 5'-flanking region modifies SP1 transcription factor binding affinity and alters transcriptional activity of Brn-3c reporter constructs in vitro. Reporter gene assays, binding affinity studies, dominant negative SP1 experiments Gene Medium 17611044
2008 Two missense mutations in POU4F3 (p.L289F in the POU homeodomain, p.L223P in the POU-specific DNA-binding domain) cause DFNA15; both mutant proteins show partial cytoplasmic localization (vs. exclusively nuclear wild-type) and greatly reduced DNA-binding and transcriptional activation capabilities. Transient transfection, subcellular localization studies (immunofluorescence), reporter gene assays, computer structural modeling Human mutation High 18228599
2010 POU4F3 (Brn-3c) is expressed in specific subsets of retinal ganglion cell types, and conditional ablation of Brn-3c alters RGC morphologies, establishing its role in determining RGC cell type-specific morphological differentiation. Genetically-directed sparse cell labeling (Cre-loxP), conditional gene ablation, morphological analysis Vision research Medium 20826176
2010 A novel 14-bp deletion mutation in POU4F3 (c.662del14) creates a truncated protein lacking both POU domains; the truncated protein fails to localize exclusively to the nucleus (unlike wild-type) and fails to activate reporter gene expression. Mutation analysis, transient transfection, immunofluorescence localization, reporter assay Biochemical and biophysical research communications Medium 20434433
2011 Caprin-1 is a direct downstream target of POU4F3, downregulated by POU4F3 through direct protein interaction with binding sites in the Caprin-1 5' flanking sequence; Caprin-1-containing stress granules are induced in cochlear hair cells following aminoglycoside-induced damage. Subtractive hybridization screen, direct binding assay (POU4F3 to Caprin-1 5' flanking sequence), expression analysis, immunohistochemistry Journal of cell science High 21402877
2012 ATOH1, TCF3 (TFE2), and GATA3 cooperate to regulate the Pou4f3 gene through conserved binding motifs 8.2–8.5 kb 5' to the ATG; co-transfection of ATOH1 with TCF3 or GATA3 induced 2–3× more Pou4f3/GFP and myosin VIIa double-positive cells compared to ATOH1 alone. Electroporation of cochlear explants, transgenic reporter (Pou4f3/GFP), immunostaining Developmental biology Medium 22985730
2014 Nr2f2 (orphan nuclear receptor) is a direct transcriptional target of POU4F3; EMSA shows POU4F3 binds to two sites in the Nr2f2 5' flanking region, and mutation of these sites reduces the Nr2f2 reporter response to POU4F3. Subtractive hybridization, EMSA (electrophoretic mobility shift assay), reporter gene assay with site-directed mutagenesis, immunocytochemistry PloS one High 25372459
2015 Transcription factors ETV4, NMYC, and ETS2, when co-transfected with ATOH1, significantly increase Pou4f3/GFP and myosin 7A-positive cells; ChIP confirms these factors bind a conserved region immediately proximal to the Pou4f3 coding sequence. Electroporation of cochlear sensory epithelium, transgenic reporter assay, chromatin immunoprecipitation (ChIP) Molecular neurobiology Medium 25015561
2016 An 8.5-kb genomic DNA fragment 5' to the Pou4f3 start codon contains multiple enhancers targeting expression to different hair cell types at different developmental ages; separate enhancer regions between 6.5–7.2 kb and 7.2–8.5 kb control expression in vestibular HCs/neonatal basal outer HCs and inner/apical outer HCs, respectively. Transgenic reporter analysis (eGFP), deletion constructs, bioinformatics Molecular neurobiology Medium 27592349
2017 Co-activation of POU4F3 and ATOH1 promoted conversion of mature supporting cells to hair cells in adult mice; activation of POU4F3 alone also converted mature supporting cells to hair cells in vivo, placing POU4F3 in a pathway with p27Kip1, GATA3, and ATOH1 for hair cell regeneration. In vivo genetic manipulation (ectopic expression), lineage tracing, immunohistochemistry Cell reports Medium 28402854
2017 A novel missense variant p.Lys328Glu in the bipartite nuclear localization signal of POU4F3 impairs transportation of POU4F3 from the cytoplasm to the nucleus, demonstrating that the bipartite NLS is functionally required for proper nuclear import. Massively parallel sequencing, subcellular localization experiments (immunofluorescence) Scientific reports Medium 28790396
2021 POU4F3 acts as a pioneer transcription factor downstream of ATOH1; ATOH1 first stimulates expression of POU4F3, which then opens closed chromatin at ATOH1 target enhancers via pioneer activity, enabling hair cell and Merkel cell differentiation to proceed through a feed-forward epigenetic mechanism. ATAC-seq, ChIP-seq, conditional mouse genetics, in vivo reporter assays in hair cells and Merkel cells Proceedings of the National Academy of Sciences of the United States of America High 34266958
2021 Co-expression of Gfi1, Pou4f3, and Atoh1 efficiently converts cochlear supporting cells into functional hair cells expressing mature markers (Prestin, vGlut3), with patch-clamp analysis showing new HCs acquired large K+ current and ribbon synapse function resembling native inner hair cells. In vivo gene delivery, immunofluorescence, electrophysiology (patch-clamp), lineage tracing Cell reports High 33882317
2022 ATOH1 directly activates POU4F3 expression (ChIP-qPCR and dual-luciferase reporter assays), and the ATOH1/POU4F3 axis upregulates MYO7A expression, enhances supporting cell proliferation, and in an oxidative stress model reduces autophagy flux, lipid peroxidation, and Fe2+ levels. ChIP-qPCR, dual-luciferase reporter assays, lentiviral overexpression/silencing, Western blotting, immunofluorescence FASEB journal Medium 40719825
2022 Hair cell gene loci become less epigenetically accessible in non-sensory cochlear cells with increasing age, and Notch signaling from hair cells to supporting cells impedes reprogramming; a combination of ATOH1, GFI1, and POU4F3 is required to overcome these barriers to hair cell reprogramming in older animals. scRNA-seq, combined scRNA-seq and ATAC-seq, Cre-inducible mouse models eLife High 36445327
2023 POU4F3 binds to three Rbm24 enhancers in vivo (identified by in vivo mouse transgenic reporter assays); Rbm24 expression is completely repressed in Pou4f3 knockout hair cells but not in Gfi1 knockout hair cells, placing Rbm24 downstream of Pou4f3 but not Gfi1; ectopic Rbm24 alone cannot prevent hair cell degeneration in Pou4f3 knockouts. In vivo transgenic reporter assay, genetic epistasis (double mutants), conditional knockout mice eLife High 38483314
2024 Pou4f3 is required for survival of cochlear hair cells at all postnatal ages; inducible deletion of Pou4f3 from postnatal hair cells at different ages all caused elevated ABR thresholds and significant HC loss, with faster loss from immature HCs; HC loss also caused delayed loss of spiral ganglion neurons without affecting supporting cell numbers. Inducible CreER-loxP system, ABR testing, immunohistochemistry, cell counting Frontiers in cellular neuroscience High 38566840
2025 PLSCR5 is a downstream target of POU4F3 required for cochlear hair cell stereocilia homeostasis; PLSCR5 contributes to phosphatidylserine externalization in hair cell apical membranes, and Plscr5 knockout mice exhibit progressive hearing loss due to stereocilia degeneration and hair cell loss. Knockout mouse, ABR/DPOAE testing, immunostaining, phosphatidylserine externalization assay Journal of genetics and genomics Medium 40068798
2025 Pou4f3 deficiency in mice obstructs type I vestibular hair cell subtype differentiation; immature vestibular HCs fail to develop type I characteristics and HC bundle formation/cell polarity are disrupted, while type II HCs differentiate normally. Pou4f3DTR/DTR and Pou4f3CreER/CreER mouse models, immunohistochemistry, electron microscopy Neuroscience bulletin Medium 40850952
2025 Base editing of the Pou4f3Q113* allele using AAV-delivered SchABE8e in neonatal mice achieved up to 48.5% editing efficiency in vitro and near-complete hearing recovery in vivo, demonstrating that restoring POU4F3 expression is sufficient to rescue auditory function in a DFNA15 mouse model. Adenine base editor screening, AAV delivery (Anc80L65), ABR testing, in vitro and in vivo editing efficiency measurement Nature communications High 40968144

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development. Proceedings of the National Academy of Sciences of the United States of America 274 9256502
1998 Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans. Science (New York, N.Y.) 261 9506947
1998 Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells. Development (Cambridge, England) 199 9735355
2004 Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a target of the Pou4f3 deafness gene. Human molecular genetics 165 15254021
2002 Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. Development (Cambridge, England) 117 11807038
2017 In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory Cells to Hair Cells in Adult Mice. Cell reports 116 28402854
2021 Generation of mature and functional hair cells by co-expression of Gfi1, Pou4f3, and Atoh1 in the postnatal mouse cochlea. Cell reports 89 33882317
2003 Brn3c null mutant mice show long-term, incomplete retention of some afferent inner ear innervation. BMC neuroscience 89 12585968
2010 Morphologies of mouse retinal ganglion cells expressing transcription factors Brn3a, Brn3b, and Brn3c: analysis of wild type and mutant cells using genetically-directed sparse labeling. Vision research 79 20826176
2022 Cellular reprogramming with ATOH1, GFI1, and POU4F3 implicate epigenetic changes and cell-cell signaling as obstacles to hair cell regeneration in mature mammals. eLife 62 36445327
2008 Missense mutations in POU4F3 cause autosomal dominant hearing impairment DFNA15 and affect subcellular localization and DNA binding. Human mutation 57 18228599
2007 Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory but not in the vestibular system. The European journal of neuroscience 57 17331196
2021 POU4F3 pioneer activity enables ATOH1 to drive diverse mechanoreceptor differentiation through a feed-forward epigenetic mechanism. Proceedings of the National Academy of Sciences of the United States of America 55 34266958
2012 BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf Pou4f3 mutant mice. Scientific reports 52 23150788
2003 The DFNA15 deafness mutation affects POU4F3 protein stability, localization, and transcriptional activity. Molecular and cellular biology 48 14585957
2012 TFE2 and GATA3 enhance induction of POU4F3 and myosin VIIa positive cells in nonsensory cochlear epithelium by ATOH1. Developmental biology 45 22985730
2015 Transcription factors with conserved binding sites near ATOH1 on the POU4F3 gene enhance the induction of cochlear hair cells. Molecular neurobiology 38 25015561
2017 Performance of a new HPV and biomarker assay in the management of hrHPV positive women: Subanalysis of the ongoing multicenter TRACE clinical trial (n > 6,000) to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer. International journal of cancer 36 27874187
2004 Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity. Biochemical and biophysical research communications 35 15465029
2017 POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss. PloS one 32 28545070
2013 SNP linkage analysis and whole exome sequencing identify a novel POU4F3 mutation in autosomal dominant late-onset nonsyndromic hearing loss (DFNA15). PloS one 30 24260153
2024 Expression of Atoh1, Gfi1, and Pou4f3 in the mature cochlea reprograms nonsensory cells into hair cells. Proceedings of the National Academy of Sciences of the United States of America 29 38266052
1995 The neuronal nicotinic acetylcholine receptor alpha 2 subunit gene promoter is activated by the Brn-3b POU family transcription factor and not by Brn-3a or Brn-3c. The Journal of biological chemistry 29 7797498
2010 A novel frameshift mutation of POU4F3 gene associated with autosomal dominant non-syndromic hearing loss. Biochemical and biophysical research communications 27 20434433
2008 Audiometric characteristics of a Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3. Archives of otolaryngology--head & neck surgery 27 18347256
2011 Caprin-1 is a target of the deafness gene Pou4f3 and is recruited to stress granules in cochlear hair cells in response to ototoxic damage. Journal of cell science 26 21402877
2016 Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss. Journal of human genetics 25 27535032
2016 A Novel Nonsense Mutation of POU4F3 Gene Causes Autosomal Dominant Hearing Loss. Neural plasticity 24 27999687
2015 Triage of high-risk human papillomavirus-positive women by methylated POU4F3. Clinical epigenetics 23 26300990
2000 Clinical characterization of genetic hearing loss caused by a mutation in the POU4F3 transcription factor. Archives of otolaryngology--head & neck surgery 23 10807331
2017 A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss. Scientific reports 22 28790396
2014 Deletion of the entire POU4F3 gene in a familial case of autosomal dominant non-syndromic hearing loss. European journal of medical genetics 21 24556497
2022 Knockdown and mutation of Pou4f3 gene mutation promotes pyroptosis of cochleae in cisplatin-induced deafness mice by NLRP3/caspase-3/GSDME pathway. Toxicology 17 36341876
2019 Pou4f3 gene mutation promotes autophagy and apoptosis of cochlear hair cells in cisplatin-induced deafness mice. Archives of biochemistry and biophysics 17 31830441
2016 Mutation in the Hair Cell Specific Gene POU4F3 Is a Common Cause for Autosomal Dominant Nonsyndromic Hearing Loss in Chinese Hans. Neural plasticity 16 28053790
2014 Regulation of the orphan nuclear receptor Nr2f2 by the DFNA15 deafness gene Pou4f3. PloS one 15 25372459
1996 Similarities and differences among inner retinal neurons revealed by the expression of reporter transgenes controlled by Brn-3a, Brn-3b, and Brn-3c promotor sequences. Visual neuroscience 15 8903036
2016 Genetic Variation in POU4F3 and GRHL2 Associated with Noise-Induced Hearing Loss in Chinese Population: A Case-Control Study. International journal of environmental research and public health 14 27271650
2015 Triage of Atypical Glandular Cell by SOX1 and POU4F3 Methylation: A Taiwanese Gynecologic Oncology Group (TGOG) Study. PloS one 13 26057869
2023 Combinatorial Atoh1, Gfi1, Pou4f3, and Six1 gene transfer induces hair cell regeneration in the flat epithelium of mature guinea pigs. Hearing research 12 38103445
2009 Vestibular impairment in a Dutch DFNA15 family with an L289F mutation in POU4F3. Audiology & neuro-otology 12 19372648
2009 Mild and variable audiometric and vestibular features in a third DFNA15 family with a novel mutation in POU4F3. The Annals of otology, rhinology, and laryngology 12 19462854
2023 Ramifications of POU4F3 variants associated with autosomal dominant hearing loss in various molecular aspects. Scientific reports 11 37537203
2024 POU4F3 Is a Sensitive and Specific Marker of Merkel Cell Carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 10 39341281
2024 Reprogramming with Atoh1, Gfi1, and Pou4f3 promotes hair cell regeneration in the adult organ of Corti. PNAS nexus 10 39411090
2020 Four Novel Variants in POU4F3 Cause Autosomal Dominant Nonsyndromic Hearing Loss. Neural plasticity 10 32684921
2018 A Missense Mutation in POU4F3 Causes Midfrequency Hearing Loss in a Chinese ADNSHL Family. BioMed research international 10 29850532
2015 Transcriptome profiling of induced hair cells (iHCs) generated by combined expression of Gfi1, Pou4f3 and Atoh1 during embryonic stem cell differentiation. Genomics data 10 26697340
2020 Identification of two novel mutations in POU4F3 gene associated with autosomal dominant hearing loss in Chinese families. Journal of cellular and molecular medicine 9 32390314
2020 Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele. The Journal of comparative neurology 9 33135183
2016 The Promoter and Multiple Enhancers of the pou4f3 Gene Regulate Expression in Inner Ear Hair Cells. Molecular neurobiology 8 27592349
1998 The Brn-3c transcription factor contains a neuronal-specific activation domain. Neuroreport 8 9579678
2024 Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining mouse cochlear hair cell survival. eLife 7 38483314
2022 POU4F3 Acts as a Tumor Suppressor in Lung Adenocarcinoma via the Endoplasmic Reticulum Stress Signaling Pathway. Journal of Cancer 7 35069902
2024 The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing. Frontiers in cellular neuroscience 6 38566840
2007 Identification and functional analysis of common sequence variants in the DFNA15 gene, Brn-3c. Gene 6 17611044
2005 Transcriptional regulation by Barhl1 and Brn-3c in organ-of-Corti-derived cell lines. Brain research. Molecular brain research 4 16226339
2025 Optimized in vivo base editing restores auditory function in a DFNA15 mouse model. Nature communications 3 40968144
2020 Cochlear implantation in a patient with a POU4F3 mutation. Clinical case reports 3 33489177
2025 Co-overexpression of Atoh1, Pou4f3, and Gfi1 enhances the transdifferentiation of supporting cells into hair cells in the neonatal mouse utricle. Neuroscience letters 2 39884380
2025 Modulating ATOH1 and POU4F3 Pathways to Enhance Hair Cell Regeneration and Inhibit Ferroptosis in Cochlear Support Cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 40719825
2025 Pou4f3 Deficiency Obstructs the Subtype Differentiation of Vestibular Hair Cells. Neuroscience bulletin 1 40850952
2021 A Missense POU4F3 Variant Associated with Autosomal Dominant Midfrequency Hearing Loss Alters Subnuclear Localization and Transcriptional Capabilities. BioMed research international 1 34250087
2017 Erratum to "A Novel Nonsense Mutation of POU4F3 Gene Causes Autosomal Dominant Hearing Loss". Neural plasticity 1 28698811
2025 The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions. Journal of genetics and genomics = Yi chuan xue bao 0 40068798
2025 Functional Correlation of Two Novel Nonsense POU4F3 Mutations Causing Late-Onset Progressive Nonsyndromic Hearing Loss in DFNA15 Families. Molecular genetics & genomic medicine 0 40364746
2025 Identification of a novel POU4F3 frameshift variant in a Chinese family with autosomal dominant hearing loss. European journal of medical research 0 40866925
2025 POU4F3 Plus Keratin AE1/AE3 or Pan-keratin: An Optimal Sentinel Lymph Node Protocol for Merkel Cell Carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 0 41380848
2009 [Mutation screening of 20 candidate genes located in chromo-some 5q31-5q32 for DFNA52 locus]. Yi chuan = Hereditas 0 19138900
2008 Molecular modelling insights into DFNA15 mediated enhancement of POU4F3 stability. International journal of computational biology and drug design 0 20054994