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Showing POU5F1 — OCT4 is a alias.

POU5F1

POU domain, class 5, transcription factor 1 · UniProt Q01860

Length
360 aa
Mass
38.6 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 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

POU5F1/OCT4 is a POU-family transcription factor that establishes and maintains the pluripotent state by acting as a pioneer factor capable of engaging nucleosomal DNA at otherwise inaccessible regulatory elements (PMID:32327602, PMID:34354236). OCT4 operates within a self-reinforcing core network: it binds cooperatively with SOX2 at a composite sox-oct element in its own distal enhancer and in the Sox2 enhancer, forming a positive autoregulatory loop whose disruption triggers differentiation (PMID:15988017), and SOX2's essential contribution is to sustain OCT4 levels, with forced OCT4 expression rescuing Sox2-null cells (PMID:17515932). At target loci OCT4 recruits additional factors—KLF4 at the Lefty1 promoter (PMID:16954384)—and integrates signal-dependent transcription factors at low-accessibility enhancers during RA and Wnt responses (PMID:27499297), while its reciprocal repressive complex with CDX2 enforces the boundary between pluripotency and trophectoderm fate (PMID:16325584). Structurally, OCT4 binds nucleosome-occluded motifs in a position-dependent manner, using its POUHD domain as a wedge to unwrap DNA from histones, contacting the histone H3 N-terminal region near the entry/exit site, and acting in multiples to cooperatively open H1-condensed nucleosome arrays—an activity continuously required to maintain enhancer accessibility (PMID:32327602, PMID:32678275, PMID:37327775, PMID:34354236). OCT4 activity is tuned by post-translational control: ERK2 phosphorylates it at T234/S235 within the homeobox to block DNA binding (PMID:22474382), WWP2 ubiquitinates it to limit protein stability (PMID:30269953), and DAX1 binds the POU-specific domain to abolish DNA binding (PMID:19528230); reciprocally, OCT4 directly activates Dax1 transcription, creating a feedback circuit (PMID:18471437). Functionally, OCT4 represses p21 to promote cell-cycle progression in ES cells (PMID:19968627), is required for primordial germ cell specification (PMID:18395706), and is essential for maintaining the inner cell mass and NANOG expression in human and bovine blastocysts (PMID:28953884, PMID:29483258). In zebrafish the ortholog drives zygotic genome activation and germ-layer patterning (PMID:23950494, PMID:14711414). The EWSR1-POU5F1 fusion behaves as an oncogenic transcription factor with OCT4 DNA-binding specificity and elevated transactivation (PMID:17564582).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1991 Medium

    Established that OCT4 functions as a transcriptional activator able to engage the basal machinery through its POU and transactivation domains, defining its activity as a sequence-specific activator.

    Evidence Transient transfection reporter assays with domain deletion and E1A bridging in cultured cells

    PMID:1830243

    Open questions at the time
    • Used a viral bridging factor rather than endogenous coactivators
    • Did not address chromatin or nucleosomal targets
  2. 1994 Medium

    Defined how OCT4 expression itself is set, showing nuclear receptors ARP-1 and RAR negatively regulate the proximal Oct-4 promoter, placing OCT4 under upstream signal control.

    Evidence Binding and transient transfection reporter assays with promoter deletions

    PMID:8152920

    Open questions at the time
    • Promoter-reporter context only
    • In vivo relevance to embryonic regulation not tested
  3. 2004 High

    Placed the OCT4 ortholog in a developmental hierarchy, showing zebrafish Pou5f1 acts upstream of sox32 to specify endoderm, demonstrating an instructive role in germ-layer fate beyond stem cell maintenance.

    Evidence Maternal-zygotic spg mutant analysis with mRNA and Pou5f1-VP16 rescue in zebrafish

    PMID:14711414

    Open questions at the time
    • Direct vs indirect targets of sox32 induction not fully resolved
    • Mammalian endoderm relevance not addressed
  4. 2005 High

    Resolved the core pluripotency wiring, showing OCT4 and SOX2 bind cooperatively to a composite element to form a positive autoregulatory loop sustaining both genes.

    Evidence ChIP in mouse and human ES cells, in vitro binding, and RNAi knockdown

    PMID:15988017

    Open questions at the time
    • Did not establish nucleosomal binding mode
    • Full enhancer co-factor composition not defined
  5. 2005 High

    Demonstrated reciprocal antagonism between OCT4 and CDX2 as the molecular switch governing the pluripotency-versus-trophectoderm decision.

    Evidence Forced expression/repression in ES cells with Co-IP and target gene analysis

    PMID:16325584

    Open questions at the time
    • Stoichiometry and structural basis of the OCT4-CDX2 complex unknown
    • Generality across species not tested
  6. 2005 Medium

    Identified EWS as an OCT4 coactivator binding the POU domain, beginning to define the partner proteins that potentiate OCT4 transactivation.

    Evidence Bacterial two-hybrid, GST pulldown, Co-IP, colocalization, and reporter assays

    PMID:15917470

    Open questions at the time
    • Endogenous requirement in ES cells not shown by loss-of-function
    • Single-lab interaction mapping
  7. 2006 Medium

    Showed OCT4 acts combinatorially with KLF4 to activate target promoters, explaining why OCT4-SOX2 enhancers require additional context-specific mediators.

    Evidence Reporter assays, factor screening, and microarray analysis in ES cells

    PMID:16954384

    Open questions at the time
    • Single target locus (Lefty1) examined
    • Direct OCT4-KLF4 physical interaction not established
  8. 2007 High

    Established that SOX2's essential role in ES cells is to maintain OCT4 levels, ordering the network with OCT4 as the key downstream effector.

    Evidence Inducible Sox2-null ES cells rescued by forced Oct3/4 expression

    PMID:17515932

    Open questions at the time
    • Did not exclude SOX2-independent OCT4 functions
    • Mechanism of indirect OCT4 regulation by SOX2 only partly defined
  9. 2008 High

    Connected OCT4 to germ-cell fate and to a feedback circuit, showing OCT4 is required cell-autonomously for primordial germ cell specification and directly activates Dax1 transcription.

    Evidence Chimeric embryo analysis with inducible Oct3/4-null ES cells; ChIP, gel shift, and reporter assays for Dax1

    PMID:18395706 PMID:18471437

    Open questions at the time
    • Direct OCT4 PGC target genes not enumerated
    • Functional consequence of the OCT4-Dax1 loop on threshold control not quantified
  10. 2009 High

    Identified DAX1 as a direct inhibitor that binds the OCT4 POU-specific domain and abolishes DNA binding, defining a protein-level off-switch.

    Evidence Co-IP, GST pulldown, gel shift, ChIP, and reporter assays in ES cells

    PMID:19528230

    Open questions at the time
    • Physiological trigger for DAX1-mediated inhibition unclear
    • Stoichiometric regulation of the OCT4/DAX1 feedback not defined
  11. 2010 Medium

    Linked OCT4 to cell-cycle control, showing it directly represses p21 to promote G0/G1 progression in ES cells.

    Evidence Inducible Oct-4 repression, flow cytometry, domain deletion, and p21 reporter assays

    PMID:19968627

    Open questions at the time
    • Direct binding at the endogenous p21 locus only inferred from reporter
    • Single-lab study
  12. 2012 High

    Defined a kinase-driven brake on OCT4, showing ERK2 phosphorylates T234/S235 in the homeobox to interrupt DNA binding and lower reprogramming efficiency.

    Evidence Phosphoproteomics, site mutagenesis, in vitro ERK2 kinase assay, and reporter/reprogramming readouts

    PMID:22474382

    Open questions at the time
    • Upstream signals controlling ERK2-OCT4 phosphorylation in vivo not mapped
    • Other phosphosites' functions unresolved
  13. 2013 High

    Generalized OCT4 to vertebrate zygotic genome activation, showing zebrafish Pou5f1 occupies SOX-POU sites and activates the earliest zygotic genes before transcription onset.

    Evidence ChIP-seq and transcriptome analysis of MZspg mutants with transgenic rescue

    PMID:23950494

    Open questions at the time
    • Pioneer mechanism at ZGA loci not structurally resolved here
    • Mammalian ZGA role not directly tested
  14. 2016 Medium

    Showed OCT4 binds low-accessibility regions and recruits signal-dependent factors, casting it as an integrator of external differentiation signals rather than a pluripotency-only factor.

    Evidence ChIP-seq with loss/gain-of-function in genetic models and a kidney cell line

    PMID:27499297

    Open questions at the time
    • Co-regulator identity at signal-responsive sites only partly defined
    • Performed in part in a non-pluripotent cell line
  15. 2020 High

    Provided the structural mechanism of OCT4 as a pioneer factor, showing position-dependent nucleosome engagement that removes DNA from histones using a single DNA-binding domain.

    Evidence Cryo-EM at base-pair resolution with in vitro nucleosome binding and mutagenesis; complementary cryo-EM/crosslinking MS at the LIN28B enhancer

    PMID:32327602 PMID:32678275

    Open questions at the time
    • In vitro reconstitution may not capture full cellular cofactor context
    • How motif orientation maps to genome-wide outcomes unresolved
  16. 2021 High

    Dissected the temporal and structural requirements of OCT4 in stem cells, showing nucleosome binding is encoded in the DBD, must be balanced for reprogramming, and that acute OCT4 loss first collapses enhancer H3K27ac and pluripotency factor expression.

    Evidence Systematic mutagenesis with ATAC/ChIP-seq; auxin-degron rapid depletion with H3K27ac and NANOG ChIP-seq

    PMID:34143975 PMID:34354236

    Open questions at the time
    • Mechanism by which NANOG binding increases upon OCT4 loss not explained
    • Direct vs indirect enhancer effects not fully separated
  17. 2021 Medium

    Extended OCT4's embryonic role to signaling and metabolism, showing it is required for JAK/STAT activation and metabolic gene regulation in the ICM.

    Evidence Single-cell transcriptomics and quantitative immunofluorescence of OCT4-null mouse blastocysts

    PMID:33452132

    Open questions at the time
    • Direct OCT4 targets in the JAK/STAT and metabolic pathways not defined
    • Mechanistic inference from pathway-level transcriptomics
  18. 2017 High

    Revealed species-specific lineage requirements, showing human POU5F1 loss downregulates both NANOG and CDX2, contrasting with the mouse trophectoderm-restriction model.

    Evidence CRISPR-Cas9 editing of human zygotes with single-cell transcriptomics and immunofluorescence

    PMID:28953884

    Open questions at the time
    • Molecular basis of human-mouse divergence not resolved
    • Direct human OCT4 target genes not mapped
  19. 2018 High

    Confirmed the human-like requirement in a second mammal and defined OCT4 protein turnover, showing OCT4 is needed for NANOG in bovine ICM and that WWP2 ubiquitination limits OCT4 stability and reprogramming.

    Evidence CRISPR/SCNT knockout in bovine embryos; ubiquitination site mapping, in vitro ubiquitination, Wwp2-null MEFs, and reprogramming assays

    PMID:29483258 PMID:30269953

    Open questions at the time
    • Signals controlling WWP2-OCT4 turnover in vivo not defined
    • Link between OCT4 stability and H3K4 methylation only correlative in part
  20. 2023 High

    Achieved high-resolution mechanism of cooperative chromatin opening, showing three OCT4 molecules engage a pre-positioned nucleosome and use POUHD as a wedge to unwrap DNA and open H1-condensed arrays.

    Evidence High-resolution cryo-EM with biochemical nucleosome opening assays and genomic analysis

    PMID:37327775

    Open questions at the time
    • In vivo stoichiometry of multi-OCT4 binding not established
    • How cooperativity is regulated by partner factors unknown
  21. 2022 Medium

    Documented a somatic, non-pluripotency role, showing OCT4 directly regulates ABCG2 to maintain endothelial metabolic homeostasis and protect against vascular dysfunction.

    Evidence EC-specific Oct4 conditional KO mice, scRNA-seq, lineage tracing, and ChIP for ABCG2

    PMID:35325071

    Open questions at the time
    • Mechanism of OCT4 reactivation in adult endothelium unclear
    • Single-lab, single tissue context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OCT4 selects between activation and repression at a given locus, and how its pioneer nucleosome-opening activity is integrated with partner availability, post-translational state, and species-specific lineage outcomes, remains unresolved.
  • No unified model linking phosphorylation/ubiquitination state to genome-wide binding outcomes
  • Determinants of activator vs repressor behavior at individual enhancers undefined
  • Molecular basis of human/bovine vs mouse lineage divergence unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1640170 Cell Cycle 1
Partners
CDX2DAX1DPF2EWSKLF4SOX2WWP2

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Oct3/4 and Cdx2 form a protein complex in ES cells that mediates reciprocal repression of their respective target genes; Cdx2 overexpression is sufficient to generate trophoblast stem cells and can mimic Oct3/4 repression-induced TE differentiation, while Cdx2 is dispensable for TE differentiation induced by Oct3/4 repression but essential for TS cell self-renewal. Forced expression/repression experiments in ES cells, co-immunoprecipitation to detect Oct3/4-Cdx2 complex, target gene analysis Cell High 16325584
2007 Sox2's essential function in ES cells is to maintain the requisite level of Oct3/4 expression by regulating multiple transcription factors that affect Oct3/4 transcription; forced expression of Oct3/4 rescues pluripotency of Sox2-null ES cells, demonstrating that Oct3/4 is the key downstream effector of Sox2. Inducible Sox2-null ES cells, rescue experiments with forced Oct3/4 expression, gene expression analysis Nature cell biology High 17515932
2005 Oct4 and Sox2 bind cooperatively to a composite sox-oct element in the distal enhancer of Pou5f1 (Oct4 gene itself) and the Sox2 enhancer in living ES cells, forming a positive autoregulatory loop; knockdown of either factor reduces both genes' enhancer activities and causes ES cell differentiation. Chromatin immunoprecipitation (ChIP) in mouse and human ES cells, in vitro binding with ESC nuclear extracts, RNAi knockdown Molecular and cellular biology High 15988017
2020 OCT4 and SOX2 bind nucleosome-occupied motifs in a position-dependent manner: at one motif position the OCT4-SOX2 complex removes DNA from histones H2A and H3, while at an inverted motif only local DNA distortions are induced; OCT4 uses only one of its two DNA-binding domains (POUHD) at both positions. Cryo-electron microscopy structure determination, in vitro nucleosome binding assays at base-pair resolution, mutagenesis Science High 32327602
2013 Zebrafish Pou5f1 (ortholog of mammalian Oct4) occupies SOX-POU binding sites at promoters of early zygotic genes before the onset of zygotic transcription and activates the earliest zygotic genes, positioning Pou5f1 and SOX-POU sites at the center of the zygotic gene activation network in vertebrates. ChIP-seq, transcriptome analysis of MZspg mutants, transgenic rescue experiments in zebrafish Science High 23950494
2006 Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in ES cells; Klf4 acts as a mediating factor that binds specifically to the proximal element of the Lefty1 promoter and is required because the Oct3/4-Sox2-dependent Lefty1 enhancer alone cannot be activated in differentiated cells. ES cell-specific enhancer identification, functional screening of ES-specific transcription factors, reporter assays, DNA microarray analysis Molecular and cellular biology Medium 16954384
1991 Oct-4 and adenovirus E1A are sufficient for distance-independent activation of the basal transcription machinery; E1A binds to the C-terminal POU domain of Oct-4 and can serve as a bridging factor between Oct-4 and the basal initiation complex; transcriptional activation depends on the transactivation domain linked to the POU domain and conserved domain 3 of E1A. Transient transfection reporter assays, deletion analysis of Oct-4 functional domains, protein interaction studies Cell Medium 1830243
2009 Dax1 (an orphan nuclear hormone receptor) directly interacts with Oct3/4 via the POU-specific domain of Oct3/4 in ES cells; this interaction abolishes DNA binding activity of Oct3/4 as shown by pulldown and gel shift assays; Dax1 inhibits Oct3/4 binding to Nanog and Oct3/4 promoter regions and its overexpression causes ES cell differentiation. Co-immunoprecipitation, GST pulldown, gel shift assays, ChIP, reporter assays, overexpression/knockdown in ES cells Molecular and cellular biology High 19528230
2005 Ewing's sarcoma protein (EWS) interacts with Oct-4 via the POU domain of Oct-4 (with three independent binding sites on EWS), co-localizes with Oct-4 in pluripotent ES cells, and enhances Oct-4 transactivation activity; the EWS activation domain is sufficient to boost Oct-4-driven promoter activity. Bacterial two-hybrid screening, GST pulldown, co-immunoprecipitation, colocalization, reporter transactivation assays Stem cells Medium 15917470
2012 OCT4 is phosphorylated at 14 sites including T234 and S235 within the homeobox region; phosphorylation at T234/S235 negatively regulates OCT4 by interrupting sequence-specific DNA binding, reducing transcriptional activation from an OCT4-responsive reporter and decreasing reprogramming efficiency; ERK2 directly phosphorylates OCT4 at these sites in vitro. LC-MS/MS phosphoproteomics, mutagenesis of phosphorylation sites, reporter assays, reprogramming efficiency assays, in vitro kinase assays with ERK2 Proceedings of the National Academy of Sciences of the United States of America High 22474382
2010 Oct-4 controls cell-cycle progression of ES cells: Oct-4 down-regulation inhibits proliferation by blocking G0/G1 progression; the p21 gene is a direct transcriptional target of Oct-4 repression, and p21 protein levels are inversely regulated by Oct-4 in ES cells. ZHBTc4 ES cells (inducible Oct-4 repression), flow cytometry cell cycle analysis, domain deletion analysis, reporter assays for p21 The Biochemical journal Medium 19968627
2008 Oct3/4 is required for primordial germ cell (PGC) specification: ES-derived cells lacking Oct3/4 contribute to PGC precursor-like cells but fail to form PGCs in chimeric embryos; restoration of Oct3/4 expression rescues PGC specification. Chimeric embryo analysis with ZHBTc4 Oct3/4-null ES cells, doxycycline-controlled transgene system, dexamethasone-inducible rescue Developmental biology High 18395706
2017 CRISPR-Cas9 knockout of POU5F1 in human zygotes compromises blastocyst development; in POU5F1-null human cells, CDX2 (trophectoderm marker) and NANOG (epiblast marker) are both downregulated—contrasting with mouse where Pou5f1-null blastocysts maintain NANOG and only fail to maintain the blastocyst. CRISPR-Cas9 genome editing of human zygotes, single-cell transcriptomics, immunofluorescence Nature High 28953884
2018 OCT4 knockout in bovine embryos (via CRISPR/SCNT) results in absence of NANOG expression in the ICM of blastocysts while CDX2 remains restricted to TE cells; OCT4 is thus required for NANOG expression but not to suppress CDX2 in bovine ICM, mirroring human but not mouse embryology. CRISPR-Cas9 OCT4 knockout, somatic cell nuclear transfer, immunofluorescence in bovine blastocysts Proceedings of the National Academy of Sciences of the United States of America High 29483258
2021 Rapid auxin-degron-mediated OCT4 depletion shows that immediate downstream effects of OCT4 loss are reduced expression of key pluripotency factors and global depletion of H3K27ac at active enhancers; trophectoderm marker upregulation is a subsequent rather than immediate event; NANOG binding to the genome is enhanced (not reduced) upon OCT4 loss. Auxin-inducible degron system for rapid protein depletion, ChIP-seq for H3K27ac, NANOG ChIP-seq, transcriptomics Stem cell reports High 34143975
2021 OCT4 is required for activation of the JAK/STAT signaling machinery (but not most other pluripotency-associated transcription factors) in the early mouse embryo ICM; OCT4 null ICMs ectopically activate trophectoderm genes and show upregulation of the lysosomal pathway and dysregulation of glycolytic enzymes, implicating OCT4 in metabolic regulation. Single-cell transcriptomics and quantitative immunofluorescence of OCT4-null blastocysts Proceedings of the National Academy of Sciences of the United States of America Medium 33452132
2016 OCT4 binds low-accessible genomic regions and is required for proper enhancer and gene activation in response to external differentiation signals (RA/RAR:RXR or Wnt/β-catenin); OCT4 recruits co-regulators and signal-dependent transcription factors to these sites, acting as an integral component of signal-regulated transcriptional processes. Genomic approaches (ChIP-seq), loss- and gain-of-function genetic models, overexpression in kidney cell line Molecular cell Medium 27499297
2021 Nucleosome binding by OCT4 is encoded within its DNA-binding domain but can be uncoupled from free-DNA binding; stable OCT4-nucleosome interactions are continuously required for maintaining accessibility of pluripotency enhancers in stem cells; both uncoupling and enhancing nucleosome binding are detrimental to reprogramming efficiency. Systematic domain dissection/mutagenesis, ATAC-seq, ChIP-seq, reprogramming efficiency assays Nature cell biology High 34354236
2020 OCT4 binds the LIN28B distal enhancer nucleosome preferentially at sequences near the entry/exit site; OCT4 contacts the histone H3 N-terminal region (near entry/exit site) as shown by crosslinking mass spectrometry; linker histone H1 competes with OCT4 for nucleosome binding. Cryo-EM single-particle analysis, chemical mapping, crosslinking mass spectrometry, mutational analysis, in vitro nucleosome binding assays Scientific reports High 32678275
2023 High-resolution cryo-EM structures of OCT4 bound to LIN28B nucleosome reveal three OCT4s binding pre-positioned nucleosomal DNA: two use POUS domains, one uses POUS-loop-POUHD; the POUHD domain acts as a wedge to unwrap ~25 bp of DNA; multiple OCT4s cooperatively open H1-condensed nucleosome arrays. Cryo-EM structure determination, biochemical nucleosome binding and opening assays, analysis of genomic data Molecular cell High 37327775
2018 WWP2 catalyzes ubiquitination of OCT4; disruption of WWP2-mediated ubiquitination or Wwp2 ablation increases OCT4 protein stability and promotes reprogramming efficiency; elevated H3K4 methylation accompanies increased OCT4 stability; OCT4 directly activates expression of Ash2l-b, a H3K4 methyltransferase complex subunit required for reprogramming. Identification of ubiquitin conjugation sites, in vitro ubiquitination assays, Wwp2 knockout mouse embryonic fibroblasts, reprogramming efficiency assays, ChIP Stem cell reports High 30269953
2015 DPF2 (a PHD finger protein) physically interacts with OCT4 in ES cells and acts as an E3 ubiquitin ligase that assembles K48-linked polyubiquitin chains on OCT4, targeting it for proteasomal degradation; DPF2 also redistributes nuclear OCT4 independently of ubiquitination. Co-immunoprecipitation, GST pulldown, in vitro ubiquitination assay, siRNA knockdown, overexpression in 293 cells Biochimica et biophysica acta Medium 26417682
2008 Oct3/4 expression in ES cells is regulated by STAT3 and Oct3/4 itself; both STAT3 and Oct3/4 directly bind putative sites in the Dax1 promoter/enhancer region; suppression of STAT3 or Oct3/4 reduces Dax1 expression, establishing that Oct3/4 activates Dax1 transcription to maintain ES cell self-renewal. Reporter assay, ChIP, gel shift assay, siRNA knockdown Biochemical and biophysical research communications Medium 18471437
2004 Zebrafish pou5f1/pou2 (maternal and zygotic) is required for endoderm specification: maternal-zygotic spg mutants fail to maintain sox32 expression and do not express sox17, resulting in loss of endodermal tissue; Pou5f1 acts upstream of sox32 to induce sox17 in endodermal precursors; a Pou5f1-VP16 activator fusion rescues gastrulation and endoderm. Maternal-zygotic mutant (MZspg) analysis, mRNA rescue injection, Pou5f1-VP16 overexpression, gene expression analysis in zebrafish Current biology High 14711414
2011 In zebrafish, Pou5f1 acts as a transcriptional activator for dorsoventral patterning; Pou5f1 directly binds phylogenetically conserved Oct/Pou5f1 sites in the vox promoter (confirmed by ChIP and in vitro binding); Pou5f1 indirectly controls fgf8a expression (Pou5f1-En repressor induces fgf8, suggesting repression), and coordinates BMP signaling network activity. Pou5f1-VP16 and Pou5f1-En fusion overexpression in zebrafish, ChIP, in vitro DNA binding, cycloheximide treatment to distinguish direct vs indirect targets Developmental biology Medium 21621531
2006 NOBOX binds directly to NOBOX binding elements (NBEs: TAATTG, TAGTTG, TAATTA) in the Pou5f1 promoter (-426 site) and augments Pou5f1 transcriptional activity; NOBOX occupies the Pou5f1 promoter in vivo as shown by ChIP. SELEX (cyclic amplification of sequence target), mutation analysis, luciferase reporter assay, ChIP The Journal of biological chemistry Medium 16997917
1994 The proximal Oct-4 promoter contains binding sites for Sp1 and three direct repeats of an AGGTCA-like sequence; nuclear receptors ARP-1 and RAR negatively regulate Oct-4 expression by binding these elements as shown by binding and transient transfection assays. Binding assays, transient transfection reporter assays, promoter deletion analysis Nucleic acids research Medium 8152920
2013 Oct4 transiently activates Meis1a expression via direct binding to the Meis1 promoter (accompanied by histone H3 acetylation and 5-hmC), while Meis1a in turn suppresses Oct4 expression by direct association with the Oct4 promoter together with HDAC1; this crosstalk is required for neural differentiation. ChIP, luciferase reporter analysis, ectopic expression, siRNA knockdown in P19 EC cells PloS one Medium 23451132
2017 OCT4 and SOX2 function as transcriptional activators during reprogramming; substituting SOX2-VP16 for wild-type SOX2 increases reprogramming efficiency and enhancer strength, while SOX2-HP1 (repressor) eliminates reprogramming; at early reprogramming stages, DNA-bound OCT4 is embedded in putative enhancers, about half of which are created de novo. Reprogramming efficiency assays with activation/repression domain fusions, ChIP-seq at early reprogramming stages Cell reports Medium 28813671
2005 The EWSR1-POU5F1 fusion protein (from t(6;22) bone tumor) binds DNA with the same sequence specificity as Oct-4, has higher transactivation activity than parental Oct-4, induces expression of fgf-4 and nanog, and causes tumorigenic growth in nude mice when expressed in Oct-4-null ES cells, establishing the fusion as an oncogenic transcription factor. DNA binding assays, reporter assays, target gene expression analysis (fgf-4, nanog), nude mouse tumorigenicity assay with Oct-4-null ZHBTc4 ES cells The Biochemical journal Medium 17564582
2022 In endothelial cells, OCT4 directly targets the ABC transporter ABCG2; the OCT4/ABCG2 axis maintains endothelial metabolic homeostasis by regulating intracellular heme accumulation and related ROS production; EC-specific Oct4 knockout increases endothelial-to-mesenchymal transitions, plaque neovascularization, and mitochondrial dysfunction. EC-specific Oct4 conditional KO mice, single-cell RNA-seq, EC-lineage tracing, ChIP to confirm ABCG2 as direct OCT4 target Cardiovascular research Medium 35325071

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation. Cell 932 16325584
2007 Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nature cell biology 905 17515932
2005 Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 681 15882627
2001 Oct-4: gatekeeper in the beginnings of mammalian development. Stem cells (Dayton, Ohio) 619 11463946
2005 Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Molecular and cellular biology 547 15988017
2003 POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer research 516 12727846
2008 Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PloS one 404 18612434
1998 Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mechanisms of development 388 9507072
2000 Expression pattern of Oct-4 in preimplantation embryos of different species. Biology of reproduction 291 11090438
2002 Stem cell pluripotency and transcription factor Oct4. Cell research 270 12528890
2017 Genome editing reveals a role for OCT4 in human embryogenesis. Nature 266 28953884
2007 OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. International journal of cancer 223 17205510
2010 Role of Oct4 in maintaining and regaining stem cell pluripotency. Stem cell research & therapy 207 21156086
2006 Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Molecular and cellular biology 194 16954384
1998 In line with our ancestors: Oct-4 and the mammalian germ. BioEssays : news and reviews in molecular, cellular and developmental biology 191 9819561
2013 Pou5f1 transcription factor controls zygotic gene activation in vertebrates. Science (New York, N.Y.) 190 23950494
2000 Oct-4: control of totipotency and germline determination. Molecular reproduction and development 190 10694754
2020 Mechanisms of OCT4-SOX2 motif readout on nucleosomes. Science (New York, N.Y.) 187 32327602
1991 A nexus between Oct-4 and E1A: implications for gene regulation in embryonic stem cells. Cell 175 1830243
2004 Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Human reproduction (Oxford, England) 168 15105401
2005 Oct4 pseudogenes are transcribed in cancers. Biochemical and biophysical research communications 158 16229821
2014 The Oct4 protein: more than a magic stemness marker. American journal of stem cells 155 25232507
2014 Role of Oct4 in the early embryo development. Cell regeneration (London, England) 155 25408886
1998 The molecular biology of Oct-4 in the early mouse embryo. Molecular human reproduction 149 9835353
2001 Comparative analysis of human, bovine, and murine Oct-4 upstream promoter sequences. Mammalian genome : official journal of the International Mammalian Genome Society 144 11309664
2009 Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells in osteosarcoma. Cancer research 140 19584295
2000 Oct-4 expression in inner cell mass and trophectoderm of human blastocysts. Molecular human reproduction 139 11044462
2013 OCT4: dynamic DNA binding pioneers stem cell pluripotency. Biochimica et biophysica acta 126 24145198
2004 Zebrafish pou5f1/pou2, homolog of mammalian Oct4, functions in the endoderm specification cascade. Current biology : CB 126 14711414
2007 Absence of OCT4 expression in somatic tumor cell lines. Stem cells (Dayton, Ohio) 108 18032701
2018 OCT4/POU5F1 is required for NANOG expression in bovine blastocysts. Proceedings of the National Academy of Sciences of the United States of America 95 29483258
2010 Oct-4 controls cell-cycle progression of embryonic stem cells. The Biochemical journal 93 19968627
2006 From adult stem cells to cancer stem cells: Oct-4 Gene, cell-cell communication, and hormones during tumor promotion. Annals of the New York Academy of Sciences 91 17261754
2012 Phosphorylation regulates human OCT4. Proceedings of the National Academy of Sciences of the United States of America 90 22474382
2020 Inhibition of Wnt/β-catenin pathway reverses multi-drug resistance and EMT in Oct4+/Nanog+ NSCLC cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 84 32428834
2012 Concise review: Oct4 and more: the reprogramming expressway. Stem cells (Dayton, Ohio) 83 22009686
2005 EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12). Genes, chromosomes & cancer 81 15729702
2006 Oct-4 expression in human endometrium. Molecular human reproduction 76 16421218
1994 Regulation of the Oct-4 gene by nuclear receptors. Nucleic acids research 76 8152920
2018 Embryonic POU5F1 is Required for Expanded Bovine Blastocyst Formation. Scientific reports 75 29773834
2006 Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5f1 promoters. The Journal of biological chemistry 75 16997917
2010 Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development. Molecular systems biology 70 20212526
2011 Clinical implications of stem cell gene Oct-4 expression in breast cancer. Annals of surgery 68 21394007
2003 Oct-4 expression in pluripotent cells of the rhesus monkey. Biology of reproduction 68 12890723
2016 OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. Molecular cell 62 27499297
2006 Bone marrow Oct3/4+ cells differentiate into cardiac myocytes via age-dependent paracrine mechanisms. Circulation research 56 17122441
2009 Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells. Molecular and cellular biology 54 19528230
2000 The OTF3 gene polymorphism confers susceptibility to psoriasis independent of the association of HLA-Cw*0602. The Journal of investigative dermatology 52 11069619
2021 OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms. Proceedings of the National Academy of Sciences of the United States of America 50 33452132
2016 OCT-4: a novel estrogen receptor-α collaborator that promotes tamoxifen resistance in breast cancer cells. Oncogene 50 27065334
2011 Expression pattern of Oct-4, Sox2, and c-Myc in the primary culture of human dental pulp derived cells. Journal of endodontics 50 21419292
2008 Requirement of Oct3/4 function for germ cell specification. Developmental biology 50 18395706
2021 Dissecting OCT4 defines the role of nucleosome binding in pluripotency. Nature cell biology 49 34354236
2005 Stimulation of Oct-4 activity by Ewing's sarcoma protein. Stem cells (Dayton, Ohio) 47 15917470
2020 Nucleosome binding by the pioneer transcription factor OCT4. Scientific reports 44 32678275
2020 Oct-4 Enhanced the Therapeutic Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Acute Kidney Injury. Kidney & blood pressure research 43 31927554
2012 Expression of OCT3/4 in renal medullary carcinoma represents a potential diagnostic pitfall. The American journal of surgical pathology 43 22301499
2011 Expression of oct-4 and c-kit antigens in endometriosis. Fertility and sterility 43 21075367
2020 Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding. Biophysical journal 42 32027821
2013 A Pou5f1/Oct4 dependent Klf2a, Klf2b, and Klf17 regulatory sub-network contributes to EVL and ectoderm development during zebrafish embryogenesis. Developmental biology 41 24211655
2011 Implications of transcriptional factor, OCT-4, in human bladder malignancy and tumor recurrence. Medical oncology (Northwood, London, England) 41 21533858
2011 Pou5f1 contributes to dorsoventral patterning by positive regulation of vox and modulation of fgf8a expression. Developmental biology 40 21621531
2009 Promoter analysis of the rabbit POU5F1 gene and its expression in preimplantation stage embryos. BMC molecular biology 40 19732419
2006 Dicer1 expression in preimplantation mouse embryos: Involvement of Oct3/4 transcription at the blastocyst stage. Biochemical and biophysical research communications 37 17113034
2017 Crosstalks between Raf-kinase inhibitor protein and cancer stem cell transcription factors (Oct4, KLF4, Sox2, Nanog). Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34 28378634
2017 OCT4 and SOX2 Work as Transcriptional Activators in Reprogramming Human Fibroblasts. Cell reports 33 28813671
2012 Pou5f1/oct4 in pluripotency control: insights from zebrafish. Genesis (New York, N.Y. : 2000) 33 21913309
2011 Co-expression of Oct-4 and Nestin in human breast cancers. Molecular biology reports 31 22207173
2008 Stem cell-specific expression of Dax1 is conferred by STAT3 and Oct3/4 in embryonic stem cells. Biochemical and biophysical research communications 30 18471437
2023 Structural mechanism of LIN28B nucleosome targeting by OCT4. Molecular cell 29 37327775
2018 Disruption of OCT4 Ubiquitination Increases OCT4 Protein Stability and ASH2L-B-Mediated H3K4 Methylation Promoting Pluripotency Acquisition. Stem cell reports 28 30269953
2009 Inner cell mass localization of NANOG precedes OCT3/4 in rhesus monkey blastocysts. Stem cells and development 28 19537945
2022 Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction. Cardiovascular research 27 35325071
2013 Differential expression of Oct4 variants and pseudogenes in normal urothelium and urothelial cancer. The American journal of pathology 26 23933063
2020 Roles of OCT4 in pathways of embryonic development and cancer progression. Mechanisms of ageing and development 25 32531293
2014 An expressed retrogene of the master embryonic stem cell gene POU5F1 is associated with prostate cancer susceptibility. American journal of human genetics 25 24581739
2014 Expression of Ki-67, Oct-4, γ-tubulin and α-tubulin in human tooth development. Archives of oral biology 25 25062118
2013 The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells. Scientific reports 25 23549118
2016 POU5F1/Oct-4 expression in breast cancer tissue is significantly associated with non-sentinel lymph node metastasis. BMC cancer 24 26931354
2007 Aberrant expression and distribution of the OCT-4 transcription factor in seminomas. Journal of biomedical science 24 17682839
2022 Additional evidence to support OCT-4 positive VSELs and EnSCs as the elusive tissue-resident stem/progenitor cells in adult mice uterus. Stem cell research & therapy 23 35123545
2013 Involvement of crosstalk between Oct4 and Meis1a in neural cell fate decision. PloS one 22 23451132
2021 HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1. Scientific reports 21 33990627
2014 Clinical significance of the stem cell gene Oct-4 in cervical cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 24532469
2022 Counterintuitive production of tumor-suppressive secretomes from Oct4- and c-Myc-overexpressing tumor cells and MSCs. Theranostics 20 35547745
2022 OCT4 interprets and enhances nucleosome flexibility. Nucleic acids research 20 36130732
2021 Auxin-degron system identifies immediate mechanisms of OCT4. Stem cell reports 20 34143975
2020 Undifferentiated round cell sarcomas with novel SS18-POU5F1 fusions. Genes, chromosomes & cancer 20 32557980
2015 DPF2 regulates OCT4 protein level and nuclear distribution. Biochimica et biophysica acta 20 26417682
2008 Nitric oxide enhances Oct-4 expression in bone marrow stem cells and promotes endothelial differentiation. European journal of pharmacology 20 18616941
2020 Role of Oct3/4 in Cervical Cancer Tumorigenesis. Frontiers in oncology 19 32219062
2018 Differential expression of Oct3/4 in human breast cancer and normal tissues. International journal of oncology 19 29620155
2007 Expression and significance of Oct4 in bladder cancer. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 19 18231740
2022 OCT4/POU5F1 is indispensable for the lineage differentiation of the inner cell mass in bovine embryos. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 35486003
2013 Unravelling the pluripotency paradox in fetal and placental mesenchymal stem cells: Oct-4 expression and the case of The Emperor's New Clothes. Stem cell reviews and reports 18 22161644
2012 Spatial and temporal distribution of Oct-4 and acetylated H4K5 in rabbit embryos. Reproductive biomedicine online 18 22381206
2007 The EWS-Oct-4 fusion gene encodes a transforming gene. The Biochemical journal 18 17564582
2022 Olfactomedin-4 improves cutaneous wound healing by promoting skin cell proliferation and migration through POU5F1/OCT4 and ESR1 signalling cascades. Cellular and molecular life sciences : CMLS 17 35218417
2008 Participation of OCT3/4 and beta-catenin during dysgenetic gonadal malignant transformation. Cancer letters 17 18295396
1993 In situ hybridization localizes the human OTF3 to chromosome 6p21.3-->p22 and OTF3L to 12p13. Cytogenetics and cell genetics 17 8500351

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