Affinage

HES6

Transcription cofactor HES-6 · UniProt Q96HZ4

Length
224 aa
Mass
24.1 kDa
Annotated
2026-04-28
43 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HES6 is a basic helix-loop-helix (bHLH) transcriptional cofactor that acts as a central antagonist of Notch/HES1-mediated repression and promotes cell differentiation across multiple lineages including neuronal, myogenic, erythroid, and hematopoietic programs. HES6 opposes HES1 by sequestering it away from Groucho/TLE corepressors and by promoting HES1 proteasomal degradation through a mechanism dependent on the WRPW motif and CK2 phosphorylation at Ser183; HES6 itself is destabilized by SUMO-mediated ubiquitination at K27/K30, and its anti-astrogenic activity requires MAPK-dependent phosphorylation of a C-terminal SPXXSP motif (PMID:12972610, PMID:26435136, PMID:17868320). In the nucleus, HES6 interacts with CBP in PML nuclear bodies to induce p21 via p53 acetylation, physically associates with GATA1 to co-regulate erythroid gene expression through a GATA1–HES6–STAT1 positive feedback loop, and cooperates with ligand-independent androgen receptor to drive an E2F1-enriched transcriptional program in castration-resistant prostate cancer (PMID:18160400, PMID:36929421, PMID:24737870). In the zebrafish segmentation clock, HES6 serves as the obligate dimerization hub of the Her/Hes oscillatory network, with Her7 modulating network topology by sequestering HES6 availability (PMID:22278920).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Establishing HES6 as a non-DNA-binding inhibitor of HES1 resolved how proneural differentiation can proceed despite active Notch/HES1 repression: HES6 suppresses HES1 transcriptional repression and derepresses MASH1-E47 heterodimers, while proneural bHLH factors reciprocally induce HES6 expression, creating a positive-feedback loop for neurogenesis.

    Evidence Reporter assays, retroviral misexpression in mouse retina, and epistasis/ectopic expression in Xenopus embryos

    PMID:10851137 PMID:10976052

    Open questions at the time
    • Mechanism by which HES6 blocks HES1 function was not resolved at the molecular level
    • Whether HES6 operates identically in mammalian vs. amphibian neurogenesis was not directly tested
  2. 2001 High

    Demonstrating that HES6 binds Groucho/TLE1 via its WRPW motif and promotes myoblast differentiation established HES6 as a differentiation regulator beyond the nervous system, with the WRPW–TLE interaction as a key functional module.

    Evidence Yeast two-hybrid, co-immunoprecipitation, reporter assays, and dominant-negative WRPW-deleted HES6 in C2C12 myoblasts

    PMID:11551980

    Open questions at the time
    • Whether HES6 competes with HES1 for TLE binding or acts independently was unclear
    • Contribution of DNA binding vs. protein-protein interaction to myogenic function was unresolved
  3. 2002 High

    Showing that HES6 can bind ESE-box DNA yet its myogenic phenotype requires protein–protein interactions rather than DNA binding clarified that HES6 functions primarily as a cofactor, not a canonical transcription factor.

    Evidence DNA-binding assays, mutagenesis, C2C12 overexpression with cell-cycle analysis, and Xenopus microinjection

    PMID:11959828

    Open questions at the time
    • In vivo relevance of ESE-box binding remained unclear
    • Distinction between pro-differentiation and anti-differentiation effects in different cellular contexts was not reconciled
  4. 2003 High

    Identifying the dual mechanism—sequestration of HES1 from GRO/TLE and promotion of HES1 proteolytic degradation—explained how HES6 achieves potent HES1 antagonism, with WRPW and CK2-dependent Ser183 phosphorylation regulating the degradation arm.

    Evidence Co-immunoprecipitation, mutagenesis of WRPW and Ser183, Western blotting for HES1 protein levels in cortical neural progenitors

    PMID:12972610

    Open questions at the time
    • Identity of the protease or E3 ligase mediating HES1 degradation was not determined
    • Whether CK2 phosphorylation of Ser183 is dynamically regulated in vivo was not tested
  5. 2005 High

    Establishing that the WRPW motif is a transferable degradation signal for HES6 itself revealed an intrinsic instability mechanism, while cross-repression between HES6 and HES5 defined a regulatory circuit controlling Notch pathway output in differentiating neurons.

    Evidence Protein stability assays with proteasome inhibitors and WRPW-fusion constructs; ectopic expression and epistasis in chick neural tissue

    PMID:15893982 PMID:15896295

    Open questions at the time
    • The E3 ubiquitin ligase targeting WRPW-containing proteins was not identified
    • Quantitative dynamics of the HES5/HES6 cross-repression were not modeled
  6. 2006 High

    Dissecting domain requirements showed that HES6 inhibits astrocyte differentiation independently of its DNA-binding basic domain but dependently on nuclear localization, the LNHLL motif, and the WRPW motif, revealing separable proneuronal and anti-gliogenic functional modules.

    Evidence siRNA knockdown and domain mutagenesis in cortical progenitors with GFAP and neuronal marker immunofluorescence

    PMID:17065448

    Open questions at the time
    • Identity of the binding partner engaged by the LNHLL motif was not established
    • Chromatin-level mechanism of gliogenic gene repression was unknown
  7. 2007 High

    Three advances converged: (1) HES6 homodimerization was shown to be the functionally relevant species for anti-astrogenic activity, regulated by MAPK phosphorylation of SPXXSP; (2) HES6 was placed downstream of FGF for XmyoD induction via Groucho relief; and (3) HES6 was localized to PML nuclear bodies where it interacts with CBP to induce p21 through p53 acetylation, connecting HES6 to cell-cycle arrest.

    Evidence Co-IP dimerization and MAPK phosphorylation assays in cortical progenitors; morpholino knockdown and Groucho Co-IP in Xenopus; Co-IP/co-localization with CBP in PML-NBs, p53 acetylation and p21 reporter assays

    PMID:17868320 PMID:17950722 PMID:18160400

    Open questions at the time
    • Whether MAPK and CK2 phosphorylation events cooperate or are context-specific was not resolved
    • Structural basis for HES6 homodimerization preference was lacking
  8. 2009 Medium

    Demonstrating that HES6 overexpression induces p53/Bax-dependent neuronal apoptosis independently of its transactivation capacity linked HES6 to apoptotic signaling, suggesting non-transcriptional mechanisms contribute to cell-fate decisions.

    Evidence Overexpression in primary cortical neurons from p53−/− and Bax−/− mice, transactivation-defective mutants

    PMID:19968968

    Open questions at the time
    • The non-transcriptional mechanism triggering apoptosis was not identified
    • Physiological context for endogenous HES6-driven apoptosis was not established
  9. 2010 Medium

    Distinguishing two HES6 subgroups (HES6-1 sequesters HES proteins; HES6-2 directly represses Hes genes by DNA binding) showed that paralogous HES6 isoforms use complementary mechanisms to progressively shut down Notch-mediated progenitor maintenance.

    Evidence Ectopic expression in chick neural tube, reporter assays, DNA-binding-deficient mutagenesis

    PMID:21151987

    Open questions at the time
    • Whether mammalian HES6 isoforms show equivalent functional divergence was not tested
    • Temporal coordination of the two subgroups in vivo was not resolved
  10. 2011 High

    ChIP-confirmed direct regulation of HES6 by MyoD/Myf5, and HES6 knockdown revealing disrupted F-actin organization and impaired myoblast fusion, placed HES6 as a cytoskeletal organizer during terminal myogenesis rather than solely a transcriptional repressor.

    Evidence ChIP for MyoD/Myf5 at the Hes6 locus, siRNA knockdown with phalloidin staining and cell motility assays in C2C12 cells, rescue with siRNA-resistant cDNA

    PMID:21501606

    Open questions at the time
    • Mechanism linking nuclear HES6 to cytoplasmic F-actin remodeling was unknown
    • Downstream effectors mediating the fusion defect were not identified beyond actin phenotype
  11. 2012 High

    Identifying HES6 as the obligate dimerization hub of the zebrafish segmentation clock Her/Hes network, with Her7 sequestering HES6 to modulate network topology, provided a systems-level understanding of how HES6 protein interactions set oscillatory dynamics.

    Evidence In vitro dimerization and DNA-binding assays, zebrafish genetics, computational network modeling

    PMID:22278920

    Open questions at the time
    • Whether mammalian HES6 plays an analogous hub role in the somite clock was not demonstrated
    • Post-translational regulation of dimerization affinities in vivo was not measured
  12. 2012 Medium

    Linking HES6 to TAGLN-dependent cell motility in rhabdomyosarcoma and to circadian LDLR regulation via CLOCK/BMAL1-driven E-box oscillation broadened HES6's functional scope to cancer cell migration and lipid metabolism.

    Evidence siRNA knockdown and TAGLN epistasis in ARMS cells; reporter assays in HepG2, HES6 mRNA oscillation in per1/per2 double-KO mice

    PMID:22913986 PMID:22982728

    Open questions at the time
    • Direct HES6 binding to TAGLN regulatory regions was not shown
    • Whether HES6 circadian oscillation functionally impacts hepatic lipid metabolism was not tested
  13. 2014 High

    Demonstrating that HES6 enhances ligand-independent androgen receptor activity and redirects AR to E2F1-enriched regulatory sites established a mechanistic basis for HES6-driven castration-resistant prostate cancer, with PLK1 inhibition as a therapeutic vulnerability.

    Evidence HES6 overexpression/knockdown in prostate cancer cells, AR ChIP-seq, xenograft tumor assays, PLK1 inhibitor treatment

    PMID:24737870

    Open questions at the time
    • Direct physical interaction between HES6 and AR was not demonstrated
    • Mechanism by which HES6 redirects AR to E2F1 sites was not resolved
  14. 2015 Medium

    Identifying sumoylation at K27/K30 as a signal for HES6 ubiquitination and proteasomal degradation, and showing that sumoylation modulates HES6 oscillation period and derepresses HES1 targets, integrated post-translational control with oscillatory gene expression dynamics.

    Evidence SUMO/HES6 co-IP, K27R/K30R mutagenesis, SUSP1 co-expression, GFP-HES6 oscillation imaging in NIH 3T3 cells

    PMID:26435136

    Open questions at the time
    • The E3 SUMO ligase and ubiquitin ligase responsible were not identified
    • Whether sumoylation regulates HES6 in the segmentation clock context was not tested
  15. 2023 High

    Demonstrating a direct HES6–GATA1 physical interaction and a GATA1–HES6–STAT1 positive feedback loop in erythroid progenitors, with EPO-driven induction, established HES6 as a regulator of erythropoiesis beyond its known neuronal and myogenic roles.

    Evidence Co-immunoprecipitation of HES6 with GATA1/FOG1, ChIP-seq, RNA-seq in erythroid progenitors, JAK2V617F mouse model

    PMID:36929421

    Open questions at the time
    • Whether HES6 modulates GATA1–FOG1 interaction stoichiometry in a functionally significant manner was not quantified
    • Contribution of HES6 to myeloproliferative disease phenotypes was not mechanistically dissected
  16. 2024 High

    Demonstrating that HES6 knockdown broadly impairs multilineage hematopoietic differentiation and competitive reconstitution established HES6 as a general regulator of hematopoietic stem/progenitor cell function, not restricted to erythropoiesis.

    Evidence shRNA knockdown in cord-blood HSPCs, in vitro multilineage differentiation, competitive transplantation in mice, single-cell RNA-seq

    PMID:38572564

    Open questions at the time
    • Mechanism by which HES6 controls HSPC self-renewal vs. differentiation balance was not defined
    • Direct transcriptional targets in HSPCs were not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • The E3 ubiquitin ligase(s) that target WRPW-containing HES6 and HES1 for proteasomal degradation remain unidentified, the structural basis for HES6's preferential homodimerization is unknown, and whether HES6's diverse tissue-specific functions (neurogenesis, myogenesis, erythropoiesis, prostate cancer) operate through a unified WRPW/TLE-dependent mechanism or fundamentally different interaction modules has not been resolved.
  • E3 ligase identity for WRPW-dependent degradation
  • Structural model of HES6 homodimer vs. heterodimer
  • Unified vs. context-dependent mechanism across tissue types

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9909396 Circadian clock 1
Partners
CBPFOG1GATA1HER7HES1RELATLE1
Complex memberships
PML nuclear body

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 HES6 alone does not bind DNA but suppresses HES1 from repressing transcription, and suppresses HES1 from inhibiting MASH1-E47 heterodimer, thereby enabling MASH1 and E47 to upregulate transcription in the presence of HES1. Mutation analysis revealed that the loop region of HES proteins plays an important role in specific functions. Transfection reporter assays, retroviral misexpression in developing retina, mutagenesis of loop region Development High 10851137
2000 HES6 expression is induced by proneural bHLH proteins (neurogenins) but not by the Notch pathway, and ectopic HES6 expression in Xenopus embryos promotes neurogenesis, placing HES6 in a positive feedback loop with proneural bHLH proteins. In situ hybridization, ectopic expression in Xenopus embryos, epistasis analysis Development High 10976052
2003 HES6 antagonizes HES1 function by two mechanisms: (1) inhibiting the interaction of HES1 with its transcriptional corepressor GRO/TLE, and (2) promoting proteolytic degradation of HES1. The effect on HES1 degradation is maximal when both proteins contain the WRPW motif and is reduced when HES6 Ser183 (a CK2 phosphorylation site) is mutated. Co-immunoprecipitation, transfection reporter assays in cortical neural progenitor cells, mutagenesis of WRPW motif and Ser183, Western blotting for protein levels Molecular and cellular biology High 12972610
2001 HES6 interacts with the corepressor TLE1 (Groucho) through its WRPW C-terminal motif in both yeast and mammalian cells. HES6 represses transcription from N-box-containing templates and cooperates with HES1 for maximal repression. HES6 expression induces myoblast differentiation and inhibits MyoR, a repressor of myogenesis; dominant-negative WRPW-deleted HES6 blocks the muscle development program. Yeast two-hybrid, co-immunoprecipitation, reporter assays, GAL4-fusion tethering, stable transfection/dominant-negative in C2C12 cells The Journal of cell biology High 11551980
2002 HES6 binds DNA containing the Enhancer of Split E box (ESE) motif and represses transcription from an ESE box reporter. Overexpression in C2C12 cells impairs differentiation, decreasing p21Cip1 induction and increasing re-entry into the cell cycle. In Xenopus, HES6 microinjection expands the myotome but suppresses terminal differentiation; mutagenesis shows DNA-binding is not essential but protein-protein interactions are required for the myogenic phenotype. DNA binding assays (ESE box), reporter assays, C2C12 overexpression, cell cycle analysis, Xenopus microinjection, mutagenesis Development High 11959828
2005 HES6-2 (chick) represses transcription of hes5 genes, functioning as a negative regulator of Notch signaling. Conversely, hes5 activity can repress hes6-2. Proneural genes upregulate hes6-2, which then prevents Notch activity in differentiating cells, forming a hes5/hes6 circuitry of negative cross-regulation. In situ hybridization, ectopic expression, epistasis analysis in chick neural tissue Developmental biology Medium 15893982
2005 The WRPW motif of HES6 acts as a degradation signal mediating proteasomal degradation; deletion of the WRPW motif substantially stabilizes HES6, and fusion of the WRPW motif to heterologous proteins (GFP, Gal4 DBD) is sufficient to destabilize them. Protein stability assays, proteasome inhibitor treatment, WRPW deletion mutagenesis, GFP- and Gal4-WRPW fusion proteins Biochemical and biophysical research communications High 15896295
2006 HES6 knockdown causes cortical progenitors to adopt astrocytic morphology and express GFAP, while exogenous HES6 inhibits astrocyte differentiation. Neither the proneuronal nor anti-gliogenic functions depend on HES6 DNA-binding via the basic arm, but both require nuclear localization; only the anti-gliogenic function depends on LNHLL and WRPW peptides. Nuclear localization is required for both activities. siRNA knockdown, exogenous expression, mutagenesis of basic domain/LNHLL/WRPW, immunofluorescence for GFAP and neuronal markers in cortical progenitors The Journal of neuroscience High 17065448
2007 HES6 preferentially forms homodimers; heterodimerization with HES1 is antagonized in part by a conserved N-terminal patch of negatively charged residues. A C-terminal SPXXSP motif is phosphorylated by the MAPK pathway and is required for anti-astrogenic activity of HES6 but not for suppression of HES1. Thus, HES6 homodimers regulate astrocyte differentiation through MAPK-dependent phosphorylation of the C-terminal domain. Co-immunoprecipitation for dimerization, mutagenesis of N-terminal patch and C-terminal SPXXSP, MAPK phosphorylation assays, cortical progenitor differentiation assays Journal of neurochemistry High 17868320
2007 HES6 is required for FGF-mediated induction of XmyoD expression in Xenopus gastrulae. The WRPW domain of HES6 (which binds Groucho/TLE co-regulators) is essential for this activity. HES6 binds Groucho proteins Xgrg2 and Xgrg4 and relieves their inhibition of XmyoD expression. Morpholino knockdown in Xenopus, co-immunoprecipitation of HES6 with Groucho proteins, WRPW mutagenesis, FGF pathway epistasis Developmental biology High 17950722
2007 HES6 is a component of the PML nuclear body complex and directly interacts with CBP (CREB-binding protein) via its basic domain. This HES6-CBP interaction inhibits cell proliferation by inducing p21 CDK inhibitor through chromatin remodeling and p53 acetylation. Co-immunoprecipitation, co-localization/immunofluorescence in PML-NBs, basic domain mutagenesis, p21 reporter and Western blot, p53 acetylation assay The Journal of biological chemistry High 18160400
2009 Overexpression of HES6 induces apoptosis in primary cultured cortical neurons via p53- and Bax-dependent pathways; neuronal apoptosis is markedly blunted in p53-/- or Bax-/- neurons. Transactivation-defective HES6 mutants also enhance neuronal apoptosis, indicating the apoptogenic activity is not directly tied to transcriptional regulation. Overexpression in primary cultured cortical neurons, apoptosis assays, p53-/- and Bax-/- knockout neurons, transactivation-defective mutants Brain research Medium 19968968
2011 HES6 is a direct transcriptional target of the myogenic factors MyoD and Myf5. HES6 protein becomes predominantly nuclear during differentiation. Knockdown of HES6 in C2C12 myoblasts disrupts F-actin filament formation and reduces cell motility and myoblast fusion without affecting cell cycle exit or myosin heavy chain induction. ChIP for MyoD/Myf5 binding to Hes6 locus, siRNA knockdown, immunofluorescence for Hes6 localization, phalloidin staining for F-actin, cell motility assay, rescue with siRNA-resistant cDNA Experimental cell research High 21501606
2011 Xenopus HES6 is essential for neurogenesis in vivo: morpholino depletion blocks neural differentiation, rescued by wild-type HES6 or a DNA-binding-deficient mutant but only partially by a Groucho/TLE-binding-deficient (WRPW-mutant) HES6. HES6 promotes neurogenesis by inhibiting anti-neurogenic Xhairy proteins and through interaction with Groucho/TLE family proteins. Morpholino antisense knockdown in Xenopus, rescue with wild-type and mutant HES6 constructs, in vivo neurogenesis assays PloS one High 22114720
2012 In the zebrafish segmentation clock, HES6 serves as the dimerization hub of the Her/Hes protein network. Her1, Her12, Her15, and Her7 each dimerize with HES6 with different affinities and DNA-binding preferences. Her7 sequesters HES6 and thereby modulates network topology by reducing HES6 availability for other heterodimers. In vitro dimerization assays, DNA-binding assays, genetic experiments in zebrafish, computational network modeling Development High 22278920
2012 HES6 knockdown in alveolar rhabdomyosarcoma (ARMSp) cells reduces proliferation and cell motility. The motility defect is associated with decreased Transgelin (TAGLN) expression; TAGLN knockdown recapitulates the motility defect and TAGLN overexpression rescues it, placing TAGLN downstream of HES6 in regulation of actin cytoskeleton and motility. siRNA knockdown, rescue with mouse Hes6 (siRNA-resistant), expression microarray, TAGLN knockdown and overexpression, cell motility assays Experimental cell research Medium 22982728
2012 HES6 and HES1 regulate the human LDLR promoter in a circadian context: CLOCK/BMAL1 upregulates LDLR promoter activity while HES1 and HES6 downregulate it under serum-depleted conditions. The repressive effect of HES1 maps to the SRE element. HES6 mRNA oscillates anti-phasically to HES1 mRNA in wild-type but not per1-/-per2-/- mice; CLOCK/BMAL1 induces HES6 via a conserved E-box in exon IV. Reporter assays in HepG2 cells, site-directed mutagenesis of SRE and E-box elements, qRT-PCR in mouse tissues, transfection in per1/per2 double-KO mice Experimental & molecular medicine Medium 22913986
2013 HES6 physically and functionally interacts with RelA-containing NF-κB complexes in cortical progenitor cells. NF-κB is selectively activated in neocortical neural progenitors and its blockade leads to premature neuronal differentiation; HES6 antagonizes NF-κB's pro-progenitor effect, and NF-κB in turn inhibits HES6's proneuronal activity. Co-immunoprecipitation of HES6 with RelA, NF-κB blockade and activation in cortical progenitors, neurogenesis assays, epistasis analysis Molecular and cellular biology Medium 23689134
2014 HES6 enhances the transcriptional activity of the androgen receptor (AR) in the absence of ligand, preferentially directing AR to a regulatory network enriched for E2F1 transcription factor binding sites, driving castration-resistant prostate cancer growth. PLK1 inhibition can pharmacologically target this HES6-AR-E2F1 axis. Overexpression and knockdown of HES6 in prostate cancer cells, AR ChIP-seq, gene expression profiling, xenograft tumor growth assays, pharmacological PLK1 inhibition EMBO molecular medicine High 24737870
2015 HES6 sumoylation occurs at lysine residues K27 and K30; sumoylation decreases HES6 protein stability by promoting ubiquitination and proteasomal degradation. Sumoylation also regulates the oscillatory period of HES6 expression and derepresses HES1-induced transcriptional repression. Overexpression of SUMO and HES6 in HeLa cells, co-immunoprecipitation, Western blotting, site-directed mutagenesis (K27R/K30R), SUMO protease SUSP1 co-expression, luciferase reporter assays for HES1 repression, GFP-HES6 oscillation imaging in NIH 3T3 cells Endocrinology and metabolism Medium 26435136
2010 Two subgroups of HES6 proteins (HES6-1 and HES6-2) function through distinct mechanisms: cHES6-2 represses transcription of Hes genes by DNA-binding and transcriptional repression; cHES6-1 sequesters other HES proteins and inhibits their activity as transcriptional repressors without requiring DNA binding. Together they progressively shut down Notch-mediated progenitor programming. Ectopic expression in chick embryonic neural tube, reporter assays for cDelta1 and cHes5, mutagenesis for DNA-binding deficiency, epistasis with Notch pathway PloS one Medium 21151987
2023 HES6 physically interacts with GATA1 and influences the interaction of GATA1 with FOG1. HES6 knockdown impairs human erythropoiesis by decreasing GATA1 expression. ChIP-seq and RNA-seq revealed co-regulated erythroid genes. A positive feedback loop composed of HES6, GATA1, and STAT1 regulates erythropoiesis, and EPO stimulation upregulates all loop components. Co-immunoprecipitation of HES6 with GATA1/FOG1, ChIP-seq, RNA-seq, siRNA knockdown in erythroid progenitors, in vivo mouse model with JAK2V617F Nucleic acids research High 36929421
2024 HES6 knockdown in cord blood-derived hematopoietic precursors reduces differentiation toward megakaryocytes, erythrocytes, plasmacytoid dendritic cells, B cells, and T cells in vitro. In vivo, HES6 knockdown HSPCs show impaired hematopoietic reconstitution in competitive transplantation. Loss of HES6 impacts cell cycle progression during erythroid differentiation. siRNA/shRNA knockdown in human cord blood HSCs, in vitro lineage differentiation assays, competitive transplantation in mice, single-cell RNA-seq, colony-forming unit assay Haematologica High 38572564
2017 The lncRNA lncSHRG recruits the chromatin organizer SATB1 to bind the HES6 promoter and initiates HES6 expression, promoting hepatocellular carcinoma cell proliferation. ChIP assay showing SATB1 binding to HES6 promoter, lncSHRG knockdown, HES6 overexpression/knockdown, in vivo tumor propagation in mice Oncotarget Medium 29050307

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation. Development (Cambridge, England) 215 10851137
2000 Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development (Cambridge, England) 118 10976052
2003 Hes6 promotes cortical neurogenesis and inhibits Hes1 transcription repression activity by multiple mechanisms. Molecular and cellular biology 102 12972610
2005 A novel hes5/hes6 circuitry of negative regulation controls Notch activity during neurogenesis. Developmental biology 94 15893982
2021 Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease. Cell death and differentiation 75 33462406
2014 HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network. EMBO molecular medicine 69 24737870
2002 Hes6 regulates myogenic differentiation. Development (Cambridge, England) 59 11959828
2006 Hes6 inhibits astrocyte differentiation and promotes neurogenesis through different mechanisms. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 17065448
2001 HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program. The Journal of cell biology 53 11551980
2012 The Her7 node modulates the network topology of the zebrafish segmentation clock via sequestration of the Hes6 hub. Development (Cambridge, England) 39 22278920
2012 Circadian regulation of low density lipoprotein receptor promoter activity by CLOCK/BMAL1, Hes1 and Hes6. Experimental & molecular medicine 38 22913986
2022 Exploring the effect of Weifuchun capsule on the toll-like receptor pathway mediated HES6 and immune regulation against chronic atrophic gastritis. Journal of ethnopharmacology 32 36403744
2017 LncSHRG promotes hepatocellular carcinoma progression by activating HES6. Oncotarget 32 29050307
2006 The bHLH transcription factors, Hes6 and Mash1, are expressed in distinct subsets of cells within adult mouse taste buds. Archives of histology and cytology 31 17031025
2011 HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation. Oncogene 30 21785461
2000 Expression of hes6, a new member of the Hairy/Enhancer-of-split family, in mouse development. Mechanisms of development 30 10906477
2009 Hes-6, an inhibitor of Hes-1, is regulated by 17beta-estradiol and promotes breast cancer cell proliferation. Breast cancer research : BCR 26 19891787
2000 Expression of mouse HES-6, a new member of the Hairy/Enhancer of split family of bHLH transcription factors. Mechanisms of development 24 11044617
2006 Basic helix-loop-helix gene Hes6 delineates the sensory hair cell lineage in the inner ear. Developmental dynamics : an official publication of the American Association of Anatomists 23 16534784
2003 Expression of Hes6 and NeuroD in the olfactory epithelium, vomeronasal organ and non-sensory patches. Chemical senses 23 12714442
2023 The novel GATA1-interacting protein HES6 is an essential transcriptional cofactor for human erythropoiesis. Nucleic acids research 20 36929421
2015 HES6 promotes prostate cancer aggressiveness independently of Notch signalling. Journal of cellular and molecular medicine 20 25864518
2013 Interaction and antagonistic roles of NF-κB and Hes6 in the regulation of cortical neurogenesis. Molecular and cellular biology 20 23689134
2007 Inhibition of cortical astrocyte differentiation by Hes6 requires amino- and carboxy-terminal motifs important for dimerization and phosphorylation. Journal of neurochemistry 20 17868320
2005 The conserved WRPW motif of Hes6 mediates proteasomal degradation. Biochemical and biophysical research communications 18 15896295
2003 Detection of differentially expressed HES-6 gene in metastatic colon carcinoma by combination of suppression subtractive hybridization and cDNA library array. Cancer letters 16 12957362
2022 Recent advances in understanding the role of HES6 in cancers. Theranostics 15 35673577
2011 Hes6 is required for the neurogenic activity of neurogenin and NeuroD. PloS one 15 22114720
2007 Hes6 is required for MyoD induction during gastrulation. Developmental biology 14 17950722
2011 Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts. Experimental cell research 12 21501606
2010 HES6-1 and HES6-2 function through different mechanisms during neuronal differentiation. PloS one 12 21151987
2007 Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body. The Journal of biological chemistry 12 18160400
2011 Cis-9,trans-11-conjugated linoleic acid promotes neuronal differentiation through regulation of Hes6 mRNA and cell cycle in cultured neural stem cells. Prostaglandins, leukotrienes, and essential fatty acids 10 21723718
2009 Induction of neuronal apoptosis by expression of Hes6 via p53-dependent pathway. Brain research 10 19968968
2012 HES6 enhances the motility of alveolar rhabdomyosarcoma cells. Experimental cell research 9 22982728
2007 HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion. Biochemical and biophysical research communications 8 17300753
2015 Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons. Cellular and molecular neurobiology 7 26105991
2015 Posterior-anterior gradient of zebrafish hes6 expression in the presomitic mesoderm is established by the combinatorial functions of the downstream enhancer and 3'UTR. Developmental biology 5 26596999
2008 Downregulation of Ccnd1 and Hes6 in rat hippocampus after chronic exposure to the antidepressant paroxetine. Acta neuropsychiatrica 5 25384412
2022 ERCC5, HES6 and RORA are potential diagnostic markers of coronary artery disease. FEBS open bio 4 35934844
2015 Sumoylation of Hes6 Regulates Protein Degradation and Hes1-Mediated Transcription. Endocrinology and metabolism (Seoul, Korea) 3 26435136
2009 Expression and association analyses of promoter variants of the neurogenic gene HES6, a candidate gene for mood disorder susceptibility and antidepressant response. Neuroscience letters 3 19481584
2024 <i>HES6</i>knockdown in human hematopoietic precursor cells reduces their <i>in vivo</i> engraftment potential and their capacity to differentiate into erythroid cells, B cells, T cells and plasmacytoid dendritic cells. Haematologica 2 38572564