Affinage

NANOG

Homeobox protein NANOG · UniProt Q9H9S0

Length
305 aa
Mass
34.6 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 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

NANOG is a divergent homeodomain transcription factor that operates at the core of the pluripotency network, directly occupying target promoters and enhancers to activate or repress lineage and self-renewal programs and to coordinate cell-fate decisions in the early embryo and germline (PMID:35871075, PMID:35729116, PMID:29320730). It homodimerizes through its C-terminal domain rather than the homeodomain, and this dimerization is required both for assembly with pluripotency network partners and for LIF-independent self-renewal (PMID:18436640); its C-terminal prion-like/intrinsically disordered region drives higher-order oligomerization and phase transition that bridges distant DNA elements, enables specific DNA recognition, and organizes transcription bodies for dose-sensitive activation of ground-state pluripotency (PMID:35484250, PMID:36476751). NANOG nucleates an activating circuitry with SALL4 and the Mediator subunit Med12 to co-regulate ES cell gene networks (PMID:16840789, PMID:19036726), and recruits TET1/TET2 to co-bound loci to deposit 5-hydroxymethylcytosine and enhance reprogramming (PMID:23395962). As a sequence-specific regulator it represses Gata6, Cdx2 and p27KIP1 and activates Esrrb and other targets, thereby suppressing endoderm/trophectoderm fate, controlling proliferation and senescence, and—through co-binding and resolution with GATA6—governing the epiblast versus primitive-endoderm decision (PMID:17615266, PMID:19564890, PMID:26795560, PMID:35871075). In germ cells NANOG is specifically required for primordial germ cell maturation, a function that the direct target Esrrb can substitute for in vivo (PMID:18097409, PMID:29320730). NANOG abundance is set by extensive post-translational control: ERK1/ERK2 and CDK1/CyclinA2 phosphorylate it, with ERK-driven phosphorylation triggering FBXW8-mediated K48-linked ubiquitination and degradation, while PKCε phosphorylation at T200/T280 stabilizes it and is required for dimerization, DNA binding and p300 recruitment to activate Bmi1 (PMID:24793005, PMID:24678451, PMID:23708658). The E3 ligase SPOP targets a NANOG degron for degradation, an event blocked by AMPK-BRAF phosphorylation at Ser68 and by Pin1, whereas USP21 deubiquitylation and the DPPA5 and TRRAP stabilizers oppose turnover—a control axis that drives prostate cancer and cancer-stem-cell traits including immune evasion via ICAM1 repression (PMID:30595538, PMID:30595535, PMID:29263902, PMID:26661329, PMID:37047234, PMID:31619256). Beyond pluripotency, NANOG governs nucleosome remodeling at zygotic genome activation and yolk syncytial layer/epiboly programs in fish embryos (PMID:30674556, PMID:29180568).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established that NANOG does not act alone but forms a positive autoregulatory circuit with a defined protein partner, framing it as a network hub rather than a solitary factor.

    Evidence Affinity-MS, reciprocal Co-IP, GST pulldown, ChIP co-occupancy and reporter assays in mouse ES cells defining the NANOG-SALL4 circuit

    PMID:16840789

    Open questions at the time
    • Did not define which NANOG domain mediates SALL4 binding
    • Did not establish genome-wide scope of co-regulated targets
  2. 2007 High

    Resolved the apparent paradox of NANOG's role by showing it is dispensable for somatic pluripotency maintenance yet specifically essential for germ-cell maturation, defining a developmental-stage-specific requirement.

    Evidence Nanog knockout chimera analysis with allelic germline rescue in mouse; ChIP at the Gata6 promoter in a separate study

    PMID:17615266 PMID:18097409

    Open questions at the time
    • Did not identify the germline target genes downstream of NANOG
    • Mechanism of stage specificity left open
  3. 2008 High

    Identified the structural basis of NANOG function by mapping C-terminal homodimerization and showing it is required for partner binding and self-renewal, and connected NANOG to the Mediator complex.

    Evidence Domain-deletion mapping with monomer/dimer constructs and self-renewal rescue; Co-IP/ChIP linking Med12 to NANOG targets in mouse ES cells

    PMID:18436640 PMID:19036726

    Open questions at the time
    • Did not show the dimer structure at atomic resolution
    • Did not distinguish direct versus Mediator-bridged partner interactions
  4. 2009 High

    Defined the transcriptional inputs and reciprocal-repression logic governing NANOG, situating it in the OCT4/SOX2/KLF4/PBX1 activation circuit and the NANOG-CDX2 mutual antagonism that enforces lineage choice.

    Evidence Promoter reporter, ChIP, EMSA and motif mutagenesis in human ES cells; ChIP and gain/loss-of-function for NANOG-CDX2 mutual repression; ChIP at the Nanog locus for Satb1/Satb2

    PMID:19522013 PMID:19564890 PMID:19933152

    Open questions at the time
    • Cross-species generality of these regulatory inputs not addressed
    • Did not quantify relative contribution of each upstream factor
  5. 2010 High

    Connected NANOG transcriptional output directly to germ-cell behavior by identifying a migration-guidance target gene whose re-expression rescues the loss-of-function phenotype.

    Evidence ChIP, morpholino knockdown and Cxcr4b mRNA rescue in medaka PGCs

    PMID:20578184

    Open questions at the time
    • Whether vertebrate orthologs use the same NANOG-Cxcr4b axis untested
    • Did not address other migration regulators
  6. 2013 High

    Revealed two distinct mechanistic layers: NANOG recruits the DNA-demethylation machinery to remodel the epigenome, and PKCε phosphorylation stabilizes NANOG and licenses its DNA-binding/coactivator functions in tumorigenesis.

    Evidence Affinity-MS/Co-IP/ChIP-seq with TET1 catalytic mutant and 5hmC quantification; PKCε kinase assay with phospho-mutants, ChIP, reporter and xenograft assays

    PMID:23395962 PMID:23708658

    Open questions at the time
    • Genome-wide rules for NANOG-directed TET recruitment incomplete
    • Functional weight of T200/T280 phosphorylation in normal pluripotency unresolved
  7. 2014 High

    Established that NANOG abundance is gated by kinase-coupled ubiquitination, with ERK/CDK1 phosphorylation feeding FBXW8-mediated proteasomal degradation that drives differentiation, and that population-level NANOG feedback governs cell-fate heterogeneity.

    Evidence In vitro kinase, Co-IP, ubiquitination and MEK-inhibitor assays in mouse ES cells; endogenous phosphosite MS with MAKS kinase-specificity mapping; single-cell profiling with genetic complementation; ChIP and BRD4/BRG1 inhibition at the Nanog locus; in vivo Cdx2/Klf4 promoter ChIP

    PMID:23103910 PMID:24678451 PMID:24793005 PMID:25146928 PMID:25173648

    Open questions at the time
    • Hierarchy among the multiple phosphosites in vivo not resolved
    • Did not reconcile FBXW8 with later-identified SPOP-dependent degradation
  8. 2015 Medium

    Identified a post-transcriptional stabilizer of NANOG protein, expanding control of NANOG levels beyond transcription and kinase signaling.

    Evidence Co-IP, protein-stability and mRNA-versus-protein dissociation assays with DPPA5 in human PSCs

    PMID:26661329

    Open questions at the time
    • Single lab without reciprocal in vivo validation
    • Did not define the DPPA5-NANOG interaction interface or the ligase it antagonizes
  9. 2016 High

    Showed that deubiquitylation actively opposes NANOG turnover and that NANOG transcriptionally represses a cell-cycle/senescence brake, linking its stability and target repression to proliferation control.

    Evidence Co-IP, domain mapping and K48 deubiquitylation assay with USP21 in mouse ES cells; ChIP at p27KIP1 with Nanog-TAT transduction and senescence assays; RIP/MS2-BioTRAP defining Nanog mRNA-binding proteins

    PMID:26289635 PMID:26795560 PMID:29263902

    Open questions at the time
    • Whether USP21 and DPPA5/FBXW8 act on overlapping pools of NANOG unknown
    • Direct versus indirect p27KIP1 repression in vivo not fully resolved
  10. 2018 High

    Defined a clinically relevant degron-and-phosphorylation switch (SPOP/AMPK-BRAF-Ser68/Pin1) controlling NANOG stability in cancer, and refined the embryonic transcriptional hierarchy and germline target logic across species.

    Evidence Co-IP/ubiquitination/degron-mutant and Pin1 assays plus tumor models for SPOP and Ser68 (two independent labs); Esrrb knockin rescue of Nanog-null PGCs; CRISPR OCT4 knockout in bovine embryos; MZnanog zebrafish mutant analysis

    PMID:29180568 PMID:29320730 PMID:29483258 PMID:30595535 PMID:30595538

    Open questions at the time
    • Interplay between SPOP and FBXW8 degradation pathways not directly compared
    • Species differences in the OCT4-NANOG-CDX2 hierarchy mechanistically unexplained
  11. 2019 Medium

    Linked NANOG to nucleosome destabilization at zygotic genome activation and to cancer immune evasion, broadening its mechanistic reach from pioneer-like chromatin opening to enhancer repression that lowers ICAM1 and NK susceptibility.

    Evidence MNase-seq in maternal-zygotic nanog/pou5f3 zebrafish mutants; ChIP-seq/RNA-seq with NANOG knockout and NK cytotoxicity/xenograft assays for ICAM1; reprogramming epistasis with LIN28/LIN41/WNT

    PMID:30674556 PMID:31619256 PMID:31806618

    Open questions at the time
    • Whether NANOG acts as a bona fide pioneer factor or cooperates with co-factors at HNARs unresolved
    • Generality of ICAM1 repression beyond prostate cancer untested
  12. 2022 High

    Provided the biophysical basis for NANOG action by showing prion-like-domain-driven oligomerization and phase transition mediate DNA bridging, transcription-body organization, and dose-sensitive ground-state pluripotency, and detailed the GATA6 co-binding/eviction mechanism of lineage segregation.

    Evidence smFRET/FCS/phase-transition reconstitution with ChIP-seq and Hi-C 3.0 and prion-like-domain mutants; live imaging of Nanog/Sox19b clustering in zebrafish; GATA6/NANOG ChIP-seq with Hi-C in ES cells and blastocysts; Nanog/Gata6 double-KO single-cell embryo analysis

    PMID:35484250 PMID:35729116 PMID:35871075 PMID:36476751

    Open questions at the time
    • In vivo dynamics and regulation of NANOG condensates incompletely defined
    • Mechanism coupling oligomerization state to target selectivity not fully resolved
  13. 2023 Medium

    Added a further stabilizing cofactor, showing TRRAP protects NANOG from FBXW8-mediated ubiquitination to sustain cancer-stem-cell traits, reinforcing degradation control as a therapeutic node.

    Evidence Co-IP with TRRAP deletion mutants, ubiquitination assay and xenograft rescue by NANOG overexpression

    PMID:37047234

    Open questions at the time
    • Single lab; reciprocal in vivo validation limited
    • Whether TRRAP acts through its known complexes or independently to block FBXW8 unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple, partly redundant degradation (FBXW8, SPOP) and stabilization (USP21, DPPA5, TRRAP, Pin1) inputs are integrated with phosphorylation and condensate state to set NANOG dosage in a given cell context remains unresolved.
  • No unified quantitative model linking NANOG abundance, oligomerization and target selection
  • Relative dominance of competing E3 ligases and stabilizers across cell types unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3
Partners
DPPA5FBXW8MED12SALL4SPOPTET1TET2USP21

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Nanog is dispensable for somatic pluripotency maintenance but specifically required for primordial germ cell maturation upon reaching the genital ridge; Nanog-null PGCs fail to mature, and this defect is rescued by repair of the mutant allele. Genetic deletion (Nanog knockout) with chimera analysis and germline rescue experiments in mouse Nature High 18097409
2008 NANOG homodimerizes through its C-terminal domain (not the homeodomain), and this dimerization is required for interaction with other pluripotency network proteins and for functional LIF-independent self-renewal of ES cells. Co-immunoprecipitation, domain deletion mapping, enforced expression of monomer vs. dimer constructs with functional self-renewal assay in mouse ES cells Proceedings of the National Academy of Sciences of the United States of America High 18436640
2006 NANOG physically interacts with SALL4 in mouse ES cells; both proteins co-occupy Nanog and Sall4 enhancer regions, and knockdown of either factor reduces enhancer activity, indicating they form a positive regulatory circuit. Affinity purification coupled to LC-MS/MS, Co-IP, GST pulldown, ChIP, RNAi knockdown with reporter assays The Journal of biological chemistry High 16840789
2013 NANOG physically associates with TET1 and TET2 in mouse ES cells; TET1 is recruited by NANOG to co-occupied genomic loci (including Esrrb and Oct4), and TET1 binding is reduced upon NANOG depletion. NANOG–TET1/TET2 interaction enhances reprogramming in a manner dependent on TET catalytic activity, increasing 5-hydroxymethylcytosine at target loci. Enhanced affinity purification/MS to identify NANOG interactors, Co-IP confirmation, ChIP-seq co-occupancy, TET1 catalytic mutant, 5hmC measurement, knockdown of TET2 in reprogramming assays Nature High 23395962
2014 ERK1 binds and phosphorylates NANOG; MEK/ERK-mediated phosphorylation decreases NANOG protein stability through ubiquitination-mediated proteasomal degradation, and induces binding of E3 ubiquitin ligase FBXW8 to NANOG, promoting its degradation and triggering ES cell differentiation. In vitro kinase assay, Co-IP, ubiquitination assay, MEK inhibitor treatment, overexpression/knockdown in mouse ES cells with self-renewal readout Stem cell research High 24793005
2018 SPOP promotes NANOG poly-ubiquitination and proteasomal degradation via a conserved degron motif on NANOG; cancer-associated SPOP mutations or Nanog-degron mutation (S68Y) disrupt this interaction and stabilize NANOG. Pin1 oncoprotein impairs NANOG recognition by SPOP, stabilizing NANOG, and Pin1 inhibitors promote SPOP-mediated NANOG destruction. Co-IP, ubiquitination assay, domain/degron mutation analysis, Pin1 interaction assay, in vivo tumor models Developmental cell High 30595535 30595538
2018 AMPK-BRAF signaling phosphorylates NANOG at Ser68, which blocks the interaction between SPOP and NANOG, thereby preventing SPOP-mediated NANOG degradation and elevating prostate cancer stemness. Phosphorylation mapping, Co-IP with SPOP-NANOG interaction assay, S68Y mutation, AMPK/BRAF manipulation in prostate cancer cells Developmental cell High 30595535
2016 USP21 deubiquitylase interacts with NANOG via its C-terminal USP domain binding to the C-domain of NANOG; USP21 removes K48-linked polyubiquitin chains from NANOG, stabilizing it. Depletion of USP21 in mouse ES cells leads to NANOG degradation and differentiation. Co-IP in vivo and in vitro, domain deletion mapping, deubiquitylation assay (K48 linkage), USP21 knockdown in mouse ES cells with NANOG protein level and pluripotency readout Signal transduction and targeted therapy High 29263902
2013 Phosphorylation of human NANOG by protein kinase Cε at T200 and T280 enhances NANOG protein stability; phosphorylation-insensitive mutants (T200A, T280A) have dominant-negative function, impairing NANOG homodimerization, DNA binding, promoter occupancy, and p300 co-activator recruitment, thereby abrogating Bmi1 transactivation. Bmi1 is identified as a critical downstream target of NANOG in tumorigenesis. Kinase assay with PKCε, phosphorylation-insensitive and phosphomimetic mutants, Co-IP for homodimerization, ChIP for DNA binding and p300 recruitment, luciferase reporter, in vivo xenograft tumor initiation assay Oncogene High 23708658
2014 Endogenous human NANOG is phosphorylated at 11 sites; ERK2 and CDK1/CyclinA2 directly phosphorylate NANOG at specific residues identified by the MAKS (multiplexed assay for kinase specificity) approach. Mass spectrometry of endogenous NANOG phosphopeptides, MAKS in vitro kinase specificity assay with site-specific identification Stem cell reports High 24678451
2008 Med12 physically interacts with NANOG in mouse ES cells; Med12 and NANOG co-occupy Nanog target promoters; Med12 knockdown phenocopies Nanog knockdown with increased expression of Nanog-repressed targets and decreased expression of Nanog-activated targets. Co-IP, ChIP, RNAi knockdown with gene expression profiling in mouse ES cells The Journal of biological chemistry Medium 19036726
2009 KLF4 directly binds the proximal NANOG promoter and PBX1 binds a new upstream enhancer and proximal promoter of NANOG in human ES cells; both factors co-operate with OCT4 and SOX2 to synergistically transactivate NANOG expression, and their knockdown or mutation of binding motifs reduces NANOG promoter activity. NANOG promoter luciferase reporter, ChIP, EMSA, overexpression/knockdown, mutagenesis of binding motifs in human ES cells Stem cells (Dayton, Ohio) High 19522013
2009 NANOG and CDX2 bind to and directly repress each other's promoters; NANOG overexpression suppresses trophectoderm markers, while NANOG knockdown upregulates TE markers. ChIP, promoter reporter assay, conditional TE differentiation ES cell line, NANOG overexpression and knockdown Cell research Medium 19564890
2007 NANOG directly binds the proximal promoter of Gata6 and represses its expression; NANOG overexpression reduces heterogeneity and Gata6-high cell frequency in mouse ES cells. ChIP at Gata6 proximal promoter, NANOG overexpression with quantitative marker analysis in mouse ES cells Stem cells (Dayton, Ohio) Medium 17615266
2022 Human NANOG contains a C-terminal prion-like domain that phase-transitions to gel-like condensates; full-length NANOG forms higher-order oligomers at low nanomolar concentrations. NANOG oligomerization is essential for bridging DNA elements in vitro, and prion-like domain assembly is required for specific DNA recognition and distant chromatin interactions in cells, providing a physical basis for chromatin reorganization and dose-sensitive activation of ground-state pluripotency. Single-molecule FRET, fluorescence cross-correlation spectroscopy, phase-transition assays, ChIP-seq, Hi-C 3.0 in cells, prion-like domain mutants Nature cell biology High 35484250
2022 In zebrafish embryos, Nanog clusters prior to transcription body formation; Nanog clustering is required for subsequent Sox19b clustering and transcription initiation. Both the DNA-binding domain and an intrinsically disordered region of Nanog are required to organize transcription bodies. Live imaging of fluorescent reporters in zebrafish embryos, mutant analysis of Nanog domains (DNA-binding domain and IDR), transcription body formation assay Current biology : CB Medium 36476751
2019 Zebrafish Nanog and Pou5f3 bind to high nucleosome affinity regions (HNARs) at zygotic genome activation; in the first step, Pou5f3 and Nanog destabilize nucleosomes at HNAR centers before ZGA; in the second step, Nanog, Pou5f3, and SoxB1 synergistically maintain open chromatin—Nanog binds to HNAR center while Pou5f3 stabilizes flanks. MNase-seq in wild-type and maternal-zygotic pou5f3 and nanog mutant zebrafish embryos, computational nucleosome occupancy modeling Genome research Medium 30674556
2010 Medaka Nanog (Ol-Nanog) is expressed in PGCs and directly regulates Cxcr4b transcription by binding its promoter; Nanog depletion causes aberrant PGC migration and loss of Cxcr4b expression; simultaneous overexpression of Cxcr4b rescues the migration defect caused by Nanog depletion. ChIP (Ol-Nanog binding to Cxcr4b promoter), morpholino knockdown of Ol-Nanog, Cxcr4b mRNA rescue experiment in medaka Stem cells (Dayton, Ohio) High 20578184
2018 In zebrafish maternal-zygotic nanog mutants, YSL formation and epiboly fail; Nanog is required for yolk microtubule organization, miR-430-mediated maternal mRNA degradation, and actin structure of the yolk syncytial layer. Cell death in MZnanog embryos is cell-autonomous. Nanog regulates spatial expression of ventral-specifying genes (bmp2b, vox, vent), neural factor her3, and degradation of maternal eomesa mRNA. Maternal-zygotic nanog mutant zebrafish analysis, chimera rescue experiments, live imaging, in situ hybridization, actin and microtubule staining Development (Cambridge, England) Medium 29180568
2016 NANOG directly occupies the p27KIP1 (CDKN1B) promoter and represses its transcription; Nanog transduction into primary fibroblasts suppresses senescence-associated β-galactosidase activity and downregulates p27KIP1, correlating with enhanced proliferation. ChIP confirming Nanog binding at p27KIP1 gene; cell-permeant Nanog-TAT protein transduction; proliferation and senescence assays in NIH 3T3 and primary fibroblasts Journal of cell science Medium 26795560
2015 DPPA5 directly interacts with NANOG protein in human PSCs, stabilizes NANOG via a post-transcriptional mechanism, and enhances NANOG function; DPPA5 overexpression increases NANOG protein levels without affecting mRNA, and DPPA5 depletion reduces NANOG. Co-immunoprecipitation, protein stability assay, quantitative RT-PCR (confirming post-transcriptional effect), overexpression/knockdown in human PSCs Stem cells (Dayton, Ohio) Medium 26661329
2012 SUMOylation of Oct4 enhances NANOG expression, while SUMOylation of Sox2 inhibits NANOG expression. Depletion of Sumo1 or its conjugating enzyme Ubc9 increases Nanog expression; high SUMOylation reduces it. SUMOylation of Oct4 by Pias2 or Sox2 by Pias3 impairs the Oct4–Sox2 interaction. SUMOylation assays, Sumo1/Ubc9 knockdown, Pias2/Pias3 overexpression, Co-IP for Oct4-Sox2 interaction, NANOG expression readout in ES cells PloS one Medium 22745796
2019 NANOG directly binds the upstream region of ICAM1 in prostate cancer cells; as NANOG binding increases, p300 binding to this region is diminished, resulting in decreased ICAM1 expression, enabling cancer cells to evade NK cell attack. ChIP-seq (NANOG and p300), RNAseq, generation of NANOG-overexpressing/knockout transformants, NK cell cytotoxicity assays, xenograft in SCID mice Journal of experimental & clinical cancer research : CR Medium 31619256
2022 GATA6 and NANOG co-bind at the vast majority of epiblast and primitive endoderm enhancers, including in blastocysts. Upon GATA6 induction, co-bound state resolves by NANOG eviction and repression of epiblast TFs, with rapid chromatin remodeling and enhancer-promoter contact changes establishing primitive endoderm lineage. ChIP-seq for GATA6 and NANOG in ES cells and blastocysts, GATA6 induction system, chromatin accessibility assays, Hi-C/enhancer-promoter contact mapping Nature communications High 35871075
2018 In bovine embryos, OCT4 is required for NANOG expression; OCT4 knockout blastocysts lack NANOG protein entirely in the ICM, while OCT4 is not required to suppress CDX2 in the ICM (contrasting with mouse). CRISPR-Cas9 OCT4 knockout in bovine fibroblasts, SCNT embryo production, immunofluorescence for NANOG, GATA6, CDX2 in blastocysts Proceedings of the National Academy of Sciences of the United States of America High 29483258
2018 Esrrb, a positively regulated direct NANOG target in ES cells, can functionally replace Nanog in PGC development in vivo; knockin of Esrrb at the Nanog locus restores PGC numbers to wild-type and yields fertile adults. Germline-specific Nanog deletion, PGCLC differentiation assay with Nanog-null ES cells, Esrrb knockin to Nanog locus, fertility assessment Cell reports High 29320730
2014 In mouse ES cells, Nanog-dependent feedback loops maintain ES cell population heterogeneity and fate decisions; early molecular changes after Nanog loss are stochastic and reversible, but prolonged Nanog absence consolidates commitment. Exogenous regulation of Nanog-dependent feedback control produces a more homogeneous ES cell population. Genetic complementation strategy, high-throughput single-cell transcriptional profiling, mathematical modeling, exogenous Nanog regulation Nature cell biology Medium 23103910
2016 YBX1 and ILF3 RNA-binding proteins interact with Nanog mRNA in mouse ES cells; knockdown of YBX1 or ILF3 reduces Nanog and other pluripotency gene expression and leads to mesoderm marker upregulation. Affinity purification of Nanog-interacting RBPs, RNA immunoprecipitation (RIP), immunofluorescence, FISH, MS2-BioTRAP, RNAi knockdown with gene expression readout Cell biology international Medium 26289635
2023 TRRAP directly binds NANOG (via TRRAP amino acids 1898–2400) and stabilizes NANOG protein by interfering with FBXW8-mediated ubiquitination; TRRAP depletion reduces cancer stem cell traits and tumor growth, which can be rescued by NANOG overexpression. Co-IP with TRRAP deletion mutants, ubiquitination assay, TRRAP knockdown/overexpression with NANOG protein stability readout, xenograft rescue experiment International journal of molecular sciences Medium 37047234
2014 Nanog ChIP analysis showed physical binding to Cdx2 and Klf4 promoters in intestinal epithelium of Nanog-inducible mice, resulting in their downregulation, increased crypt cell proliferation, and intestinal hyperplasia without tumor formation. Tet-On inducible Nanog mouse model, ChIP at Cdx2 and Klf4 promoters, histological analysis of intestinal tissue Stem cell research Medium 25173648
2019 NANOG and LIN28 drive reprogramming by activating LIN41 expression (a Let-7 miRNA target) and activating canonical WNT/β-CATENIN signaling; LIN41 can replace LIN28 synergizing with NANOG; dominant-negative LIN41 mutation blocks NANOG/LIN28-enhanced reprogramming. Reprogramming efficiency assays, pathway inhibitor treatments, dominant-negative LIN41 mutant, overexpression of LIN41 in OSKM context, measurement of WNT activation Biology open Medium 31806618
2013 In mouse ES cells, Satb1 and Satb2 both bind the Nanog locus in vivo; Satb1-deficient ES cells show increased Nanog expression and higher proportion of Nanog-high cells; Satb1 and Satb2 have antagonistic effects on Nanog expression and ES cell differentiation capacity. ChIP (Satb1 and Satb2 binding at Nanog locus), Satb1/Satb2 knockout ES cells, Satb2 overexpression, differentiation assays, cell fusion reprogramming assay Genes & development Medium 19933152
2014 BRD4 associates with BRG1 at Nanog regulatory regions in mouse ES cells to regulate Nanog expression; inhibition of BRD4 (chemically, siRNA, or dominant-negative) suppresses Nanog expression and abolishes ES cell self-renewal. ChIP (BRD4 and BRG1 at Nanog locus), BRD4 chemical inhibitor, siRNA knockdown, dominant-negative BRD4, Nanog expression and self-renewal readout Cell death and differentiation Medium 25146928
2013 CDX2 induction in mouse ES cells causes time-dependent increase in CDX2 binding and decrease in OCT4 binding at Nanog regulatory elements, loss of H3K9/14 acetylation and p300/HDAC1 binding, increased histone H3 occupancy, loss of chromatin accessibility, and only later DNA methylation at Nanog regulatory elements—demonstrating sequential epigenetic silencing of Nanog. Cdx2-inducible ES cell line, ChIP time course (CDX2, OCT4, RNAPII, H3K9/14ac, p300, HDAC1, total H3), chromatin accessibility assay, bisulfite sequencing Stem cells and development Medium 24059348
2022 NANOG triggers epiblast specification by ensuring coordinated expression of pluripotency markers; in Nanog/Gata6 double KO embryos, coordination of pluripotency markers fails, while individual marker expression remains variable in ICM progenitors. Nanog/Gata6 double knockout mouse embryo analysis, single-cell transcriptomics, immunofluorescence, analysis of human embryos Nature communications Medium 35729116

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Nanog safeguards pluripotency and mediates germline development. Nature 1138 18097409
2007 Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell research 471 17211451
2009 Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells. PLoS biology 423 19582141
2013 NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 344 23395962
2011 NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene 312 21499299
2007 A heterogeneous expression pattern for Nanog in embryonic stem cells. Stem cells (Dayton, Ohio) 284 17615266
2006 Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. The Journal of biological chemistry 234 16840789
2005 Nanog expression in mouse germ cell development. Gene expression patterns : GEP 219 15939376
2013 Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells. Cancer letters 139 23872274
2010 Nanog overcomes reprogramming barriers and induces pluripotency in minimal conditions. Current biology : CB 137 21194951
2009 Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression. Genes & development 116 19933152
2012 Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity. Nature cell biology 114 23103910
2010 Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis. Pancreas 113 20173672
2014 Emerging role of nanog in tumorigenesis and cancer stem cells. International journal of cancer 112 24375318
2004 Eleven daughters of NANOG. Genomics 112 15233988
2009 KLF4 and PBX1 directly regulate NANOG expression in human embryonic stem cells. Stem cells (Dayton, Ohio) 110 19522013
2008 Requirement of Nanog dimerization for stem cell self-renewal and pluripotency. Proceedings of the National Academy of Sciences of the United States of America 110 18436640
2003 Nanog: a new recruit to the embryonic stem cell orchestra. Cell 105 12787492
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
2009 Cross-regulation of the Nanog and Cdx2 promoters. Cell research 95 19564890
2013 Concise review: pursuing self-renewal and pluripotency with the stem cell factor Nanog. Stem cells (Dayton, Ohio) 92 23653415
2022 Nanog, as a key cancer stem cell marker in tumor progression. Gene 88 35337852
2014 ERK1 phosphorylates Nanog to regulate protein stability and stem cell self-renewal. Stem cell research 88 24793005
2015 Regulation of NANOG in cancer cells. Molecular carcinogenesis 87 26013997
2020 Inhibition of Wnt/β-catenin pathway reverses multi-drug resistance and EMT in Oct4+/Nanog+ NSCLC cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 84 32428834
2015 Association of OCT4, SOX2, and NANOG expression with oral squamous cell carcinoma progression. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 78 26211876
2018 AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness. Developmental cell 76 30595535
2021 Characterization of SOX2, OCT4 and NANOG in Ovarian Cancer Tumor-Initiating Cells. Cancers 72 33445692
2006 Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochemical and biophysical research communications 65 16540082
2018 SPOP Promotes Nanog Destruction to Suppress Stem Cell Traits and Prostate Cancer Progression. Developmental cell 63 30595538
2014 BRD4 regulates Nanog expression in mouse embryonic stem cells and preimplantation embryos. Cell death and differentiation 61 25146928
2010 Expression of NANOG and NANOGP8 in a variety of undifferentiated and differentiated human cells. The International journal of developmental biology 59 21136380
2005 Expression of Nanog gene promotes NIH3T3 cell proliferation. Biochemical and biophysical research communications 59 16259959
2011 Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells. Oncology reports 57 21573506
2022 Nanog mediated by FAO/ACLY signaling induces cellular dormancy in colorectal cancer cells. Cell death & disease 54 35177584
2019 Pou5f3, SoxB1, and Nanog remodel chromatin on high nucleosome affinity regions at zygotic genome activation. Genome research 54 30674556
2016 Insights into the Nanog gene: A propeller for stemness in primitive stem cells. International journal of biological sciences 54 27877089
2008 Role for Med12 in regulation of Nanog and Nanog target genes. The Journal of biological chemistry 54 19036726
2020 NANOG expression in human development and cancerogenesis. Experimental biology and medicine (Maywood, N.J.) 53 32041418
2020 The oncogenic potential of NANOG: An important cancer induction mediator. Journal of cellular physiology 52 32960465
2019 Epithelial cell senescence induces pulmonary fibrosis through Nanog-mediated fibroblast activation. Aging 50 31891567
2014 Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency. Nature communications 50 25284313
2011 NANOG promoter methylation and expression correlation during normal and malignant human germ cell development. Epigenetics 50 20930529
2012 Nanog and Oct4 overexpression increases motility and transmigration of melanoma cells. Journal of cancer research and clinical oncology 47 22406932
2019 NANOG is required to form the epiblast and maintain pluripotency in the bovine embryo. Molecular reproduction and development 45 31803983
2017 Epithelial-mesenchymal transition promotes SOX2 and NANOG expression in bladder cancer. Laboratory investigation; a journal of technical methods and pathology 45 28240746
2021 PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas. Oncogenesis 43 33468992
2016 USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency. Signal transduction and targeted therapy 43 29263902
2014 NANOG is multiply phosphorylated and directly modified by ERK2 and CDK1 in vitro. Stem cell reports 43 24678451
2012 SUMOylation represses Nanog expression via modulating transcription factors Oct4 and Sox2. PloS one 43 22745796
2006 Germ cell restricted expression of chick Nanog. Developmental dynamics : an official publication of the American Association of Anatomists 43 16921504
2005 The homeodomain protein Nanog and pluripotency in mouse embryonic stem cells. Biochemical Society transactions 42 16246159
2022 Extensive co-binding and rapid redistribution of NANOG and GATA6 during emergence of divergent lineages. Nature communications 40 35871075
2018 Esrrb Complementation Rescues Development of Nanog-Null Germ Cells. Cell reports 40 29320730
2013 Phosphorylation of Nanog is essential to regulate Bmi1 and promote tumorigenesis. Oncogene 40 23708658
2013 LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer. Biochemical and biophysical research communications 38 23438436
2011 Expression of the stem cell marker, Nanog, in human endometrial adenocarcinoma. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 37 21464727
2022 NANOG initiates epiblast fate through the coordination of pluripotency genes expression. Nature communications 36 35729116
2019 Nanog Signaling Mediates Radioresistance in ALDH-Positive Breast Cancer Cells. International journal of molecular sciences 34 30845764
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
2014 Slug promotes hepatocellular cancer cell progression by increasing sox2 and nanog expression. Oncology reports 32 25339068
2022 NANOG prion-like assembly mediates DNA bridging to facilitate chromatin reorganization and activation of pluripotency. Nature cell biology 31 35484250
2019 NANOG and LIN28 dramatically improve human cell reprogramming by modulating LIN41 and canonical WNT activities. Biology open 30 31806618
2018 Maternal Nanog is required for zebrafish embryo architecture and for cell viability during gastrulation. Development (Cambridge, England) 30 29180568
2017 NANOG regulates epithelial-mesenchymal transition and chemoresistance in ovarian cancer. Bioscience reports 30 27884977
2019 TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma. Molecular oncology 28 30657254
2019 NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis. Journal of experimental & clinical cancer research : CR 28 31619256
2014 Epigenetic targeting of the Nanog pathway and signaling networks during chemical carcinogenesis. Carcinogenesis 28 24480805
2022 Nanog organizes transcription bodies. Current biology : CB 27 36476751
2018 The primary role of zebrafish nanog is in extra-embryonic tissue. Development (Cambridge, England) 27 29180571
2018 Nanog induced intermediate state in regulating stem cell differentiation and reprogramming. BMC systems biology 27 29486740
2013 FAK and Nanog cross talk with p53 in cancer stem cells. Anti-cancer agents in medicinal chemistry 25 22934707
2010 Nanog regulates primordial germ cell migration through Cxcr4b. Stem cells (Dayton, Ohio) 25 20578184
2010 NANOG reporter cell lines generated by gene targeting in human embryonic stem cells. PloS one 25 20824089
2018 Differential sequences of exosomal NANOG DNA as a potential diagnostic cancer marker. PloS one 24 29787607
2015 DPPA5 Supports Pluripotency and Reprogramming by Regulating NANOG Turnover. Stem cells (Dayton, Ohio) 24 26661329
2016 Nanog induces suppression of senescence through downregulation of p27KIP1 expression. Journal of cell science 23 26795560
2020 LASP1 induces colorectal cancer proliferation and invasiveness through Hippo signaling and Nanog mediated EMT. American journal of translational research 22 33194046
2018 Inductive and Selective Effects of GSK3 and MEK Inhibition on Nanog Heterogeneity in Embryonic Stem Cells. Stem cell reports 22 29779897
2014 On the origin and evolutionary history of NANOG. PloS one 22 24465486
2010 PTEN and TRP53 independently suppress Nanog expression in spermatogonial stem cells. Stem cells and development 22 19845468
2023 Suppression of NANOG Expression Reduces Drug Resistance of Cancer Stem Cells in Glioblastoma. Genes 21 37372456
2016 Nanog RNA-binding proteins YBX1 and ILF3 affect pluripotency of embryonic stem cells. Cell biology international 21 26289635
2020 Expression of NANOG and Its Regulation in Oral Squamous Cell Carcinoma. BioMed research international 20 32733958
2013 Knockdown of p53 suppresses Nanog expression in embryonic stem cells. Biochemical and biophysical research communications 20 24333425
2018 Functional characterization of NANOG in goat pre-implantation embryonic development. Theriogenology 19 30092372
2017 Nanog Expression in Embryonic Stem Cells - An Ideal Model System to Dissect Enhancer Function. BioEssays : news and reviews in molecular, cellular and developmental biology 19 28977693
2021 The multiple faces of NANOG in cancer: a therapeutic target to chemosensitize therapy-resistant cancers. Epigenomics 18 34693722
2017 Nanog Dynamics in Mouse Embryonic Stem Cells: Results from Systems Biology Approaches. Stem cells international 18 28684962
2016 Metformin and AICAR regulate NANOG expression via the JNK pathway in HepG2 cells independently of AMPK. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 26939902
2019 MED20 is essential for early embryogenesis and regulates NANOG expression. Reproduction (Cambridge, England) 17 30571656
2014 Cell-permeant recombinant Nanog protein promotes pluripotency by inhibiting endodermal specification. Stem cell research 17 24681518
2014 Nanog induces hyperplasia without initiating tumors. Stem cell research 17 25173648
2019 FOXH1 Is Regulated by NANOG and LIN28 for Early-stage Reprogramming. Scientific reports 16 31712708
2023 TRRAP Enhances Cancer Stem Cell Characteristics by Regulating NANOG Protein Stability in Colon Cancer Cells. International journal of molecular sciences 15 37047234
2022 OCT4, SOX2 and NANOG co-regulate glycolysis and participate in somatic induced reprogramming. Cytotechnology 15 35733702
2021 Nanog promotes stem-like traits of glioblastoma cells. Frontiers in bioscience (Landmark edition) 15 33049683
2013 Transcriptional reprogramming and chromatin remodeling accompanies Oct4 and Nanog silencing in mouse trophoblast lineage. Stem cells and development 15 24059348
2021 Hypoblast Formation in Bovine Embryos Does Not Depend on NANOG. Cells 14 34571882
2017 Functional evidence that the self-renewal gene NANOG regulates esophageal squamous cancer development. Biochemical and biophysical research communications 14 28601640

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