Affinage

SPEN

Msx2-interacting protein · UniProt Q96T58

Audit flag: alt product
Length
3664 aa
Mass
402.2 kDa
Annotated
2026-04-28
100 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPEN (SHARP/MINT) is a large RNA-binding transcriptional repressor that serves as a master effector of lncRNA- and DNA-binding-factor-mediated gene silencing, functioning centrally in both X chromosome inactivation and Notch pathway repression. In X chromosome inactivation, SPEN is directly recruited to the inactive X by Xist lncRNA through its RRM domains (which recognize the Xist A-repeat and structurally similar endogenous retroviral RNAs), localizes to enhancers and promoters of active genes, and silences transcription via its SPOC domain, which recruits the NCoR/SMRT–HDAC3 corepressor axis to drive histone deacetylation and RNA Pol II exclusion; SPEN also undergoes non-stoichiometric amplification across the X through concentration-dependent homotypic assemblies and acts in parallel with Polycomb pathways (PMID:25915022, PMID:32025035, PMID:35301492, PMID:35584662, PMID:38834912). In the Notch signaling pathway, SPEN competes with the Notch intracellular domain for binding to RBPJ/CSL and assembles an HDAC-containing corepressor complex that includes SMRT, NuRD components, CtIP, and CtBP to silence Notch target genes such as HES-1 and Hey1 (PMID:12374742, PMID:12594956, PMID:16287852, PMID:30673607). Crystal structures of the SPOC domain bound to NCoR/SMRT and of the SPEN–RBPJ–DNA ternary complex define the structural basis for both repressive partnerships (PMID:12897056, PMID:30673607).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Identifying SPEN as a transcriptional repressor that bridges RNA recognition to corepressor recruitment answered how a single factor could integrate RNA-level and chromatin-level regulation.

    Evidence Yeast two-hybrid, co-IP, and cotransfection repression assays showed SHARP binds SRA RNA and recruits SMRT and NuRD complex components

    PMID:11331609

    Open questions at the time
    • Physiological RNA targets beyond SRA were unknown
    • In vivo relevance of SMRT and NuRD recruitment not yet demonstrated
  2. 2002 High

    Demonstrating that SPEN represses Notch target genes through RBPJ and HDAC-dependent mechanisms established it as a core negative regulator of the Notch pathway.

    Evidence Yeast two-hybrid, reporter assays, TSA sensitivity, and Xenopus embryo rescue of Notch-driven neurogenesis defects

    PMID:12374742

    Open questions at the time
    • Structural basis of SPEN–RBPJ interaction was unresolved
    • Identity of all corepressor complex members not defined
  3. 2003 High

    Structural determination of the SPOC domain and genetic loss-of-function in mice resolved how SPEN contacts NCoR/SMRT corepressors and confirmed its physiological role in restraining Notch signaling in vivo.

    Evidence 1.8 Å crystal structure of SPOC domain with mutagenesis (PMID:12897056); MINT-null mice showing enhanced marginal zone B cell differentiation from derepressed Notch signaling (PMID:12594956)

    PMID:12594956 PMID:12897056

    Open questions at the time
    • Full-length SPEN structure unavailable
    • How SPEN is regulated post-translationally was unknown
  4. 2005 High

    Identification of CtIP/CtBP as additional corepressor partners and Pak1-mediated phosphorylation of SPEN expanded the repression complex architecture and revealed a kinase-dependent regulatory input.

    Evidence GST pulldown, co-IP, ChIP on Hey1 promoter, CtBP-deficient cells (PMID:16287852); Pak1 phosphorylation site mapping with functional reporter assays (PMID:15824732)

    PMID:15824732 PMID:16287852

    Open questions at the time
    • Whether Pak1 phosphorylation modulates SPEN in vivo during Notch signaling was untested
    • Relative contributions of CtBP vs. SMRT/NuRD to repression were unclear
  5. 2011 High

    Quantitative biophysical measurement of the SPEN–RBPJ interaction defined the minimal domains required, setting the stage for structural understanding of the ternary DNA complex.

    Evidence Isothermal titration calorimetry and domain deletion analysis of MINT–CSL binding

    PMID:21372128

    Open questions at the time
    • Atomic-resolution ternary structure with DNA was still lacking
  6. 2015 High

    Three independent studies converged on SPEN as the essential direct effector of Xist-mediated X chromosome silencing, fundamentally repositioning the gene from a Notch pathway repressor to the central mediator of XCI.

    Evidence RAP-MS identifying SPEN as Xist-binding protein with shRNA KD abolishing Pol II exclusion and PRC2 recruitment (PMID:25915022); forward genetic screen in haploid ESCs (PMID:26190100); pooled shRNA screen with super-resolution co-localization (PMID:26190105)

    PMID:25915022 PMID:26190100 PMID:26190105

    Open questions at the time
    • Which Xist RNA element SPEN recognizes was not fully mapped
    • Mechanism by which SPEN spreads across the X was unknown
    • Role in human XCI not yet tested
  7. 2019 High

    The crystal structure of the RBPJ–SPEN–DNA ternary complex resolved the atomic-level mechanism by which SPEN docks onto the Notch pathway's DNA-binding transcription factor to enforce repression.

    Evidence X-ray crystallography, ITC, structure-based RBPJ mutagenesis with cellular reporter assays

    PMID:30673607

    Open questions at the time
    • Structure does not capture full repression complex with SMRT/NuRD
    • Dynamic regulation of complex assembly in vivo remained unclear
  8. 2020 High

    Dissection of SPEN's role in XCI at enhancers/promoters, identification of the SPOC domain as sufficient for silencing when tethered to Xist, and discovery that SPEN RRMs recognize endogenous retroviral RNAs structurally mimicking the Xist A-repeat provided a unified mechanistic model for SPEN-mediated chromatin silencing.

    Evidence Mouse genetic KOs with ChIP-seq and RNA-seq, SPOC tethering, MS proteomics of SPOC partners (PMID:32025035); CLIP-seq, ATAC-seq, ERV insertion rescue in Spen KO ESCs (PMID:32379046)

    PMID:32025035 PMID:32379046

    Open questions at the time
    • Whether ERV-SPEN interactions have genome-wide regulatory significance beyond XCI was unexplored
    • Structural basis of RRM–A-repeat recognition at atomic resolution was missing
  9. 2021 High

    Revealing that SPEN is required upstream for Xist upregulation—by silencing the antisense Tsix promoter—added a feedforward regulatory loop to the XCI initiation model.

    Evidence Spen-null ESCs with failed Xist upregulation rescued by concomitant Tsix deletion

    PMID:34853312

    Open questions at the time
    • Whether SPEN silences Tsix through the same SPOC–NCoR mechanism was not shown
    • Regulation of SPEN's own expression during XCI initiation was unclear
  10. 2022 High

    Quantitative imaging and separation-of-function genetics established that SPEN undergoes non-stoichiometric spatial amplification on the X, acts in parallel with Polycomb, and contributes to correct Xist RNA localization in cis.

    Evidence Single-molecule FISH and protein imaging with domain mutants (PMID:35301492); separation-of-function SPEN mutation with RNA-seq and epistasis (PMID:35584662)

    PMID:35301492 PMID:35584662

    Open questions at the time
    • Molecular basis of homotypic SPEN assembly was not structurally characterized
    • How SmcHD1 cooperates with SPEN mechanistically was undefined
  11. 2024 High

    Demonstrating SPEN-dependent transcriptional dampening and polycomb deposition on the human X chromosome confirmed conservation of SPEN's XCI role from mouse to human preimplantation development.

    Evidence SPEN knockout in naive human ESCs with H3K27me3 ChIP-seq and RNA-seq

    PMID:38834912

    Open questions at the time
    • Whether SPEN's non-XCI functions (Notch, ERV silencing) are conserved in human remains less explored
    • Therapeutic targeting of SPEN in X-linked disorders has not been investigated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of SPEN RRMs bound to Xist A-repeat RNA, the molecular determinants of SPEN homotypic assembly on the inactive X, the full-length structure of SPEN, and whether SPEN's ERV-silencing function has broader genome regulatory significance beyond XCI.
  • No full-length SPEN structure
  • Structural basis of RRM–Xist A-repeat recognition unresolved
  • Mechanism of homotypic SPEN amplification on Xi not structurally characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003723 RNA binding 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0000228 nuclear chromosome 6 GO:0005634 nucleus 4 GO:0005694 chromosome 4
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 5 R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5
Partners
CTBP1CTIP2HDAC1HDAC3NCOR1NCOR2PAK1RBPJ
Complex memberships
NCoR/SMRT corepressor complexNuRD complexRBPJ/CSL corepressor complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 SHARP (SPEN) was identified as a transcriptional repressor whose repression domain directly interacts with the SMRT corepressor and at least five members of the NuRD complex (including HDAC1 and HDAC2). SHARP also binds the steroid receptor RNA coactivator SRA via an intrinsic RNA binding domain and suppresses SRA-potentiated steroid receptor transcription activity. Yeast two-hybrid screen, co-immunoprecipitation, direct binding assays, cotransfection repression assays Genes & development High 11331609
2002 SHARP (SPEN) was identified as an RBP-Jkappa/CBF-1-interacting corepressor in the Notch pathway. SHARP-mediated repression of Notch target genes (e.g., HES-1) was sensitive to HDAC inhibitor TSA, was facilitated by SKIP, and rescued Notch-1-induced inhibition of primary neurogenesis in Xenopus embryos. Yeast two-hybrid screen, cotransfection reporter assays, HDAC inhibitor treatment, Xenopus embryo rescue experiments The EMBO journal High 12374742
2003 Crystal structure of the SPOC domain from SHARP (SPEN) at 1.8 Å resolution revealed that conserved surface residues map to a positively charged patch responsible for interaction with a conserved acidic motif at the C terminus of SMRT/NCoR corepressors, defining the essential transcriptional repression function of Spen proteins. X-ray crystallography (1.8 Å), structure-based mutagenesis, binding assays Genes & development High 12897056
2003 MINT (SPEN) competed with the intracellular domain of Notch for binding to RBP-J and suppressed Notch transactivation activity. MINT-deficient mice showed enhanced marginal zone B cell differentiation, consistent with de-repression of Notch signaling. Competitive binding assays, MINT null mouse genetic analysis, B cell differentiation assays Immunity High 12594956
2005 The SHARP repression domain is necessary and sufficient for transcriptional repression in the Notch pathway. CtIP and CtBP corepressors are novel components of the human RBP-Jkappa/SHARP corepressor complex; CtIP binds directly to the SHARP repression domain, and CtBP deficiency abolishes repression of the endogenous Notch target Hey1 promoter. Domain deletion/mutation assays, GST pulldown, co-immunoprecipitation, chromatin immunoprecipitation, CtBP-deficient cell analysis Molecular and cellular biology High 16287852
2005 SHARP is a physiological substrate of Pak1 kinase. Pak1 directly phosphorylates SHARP at Ser3486 and Thr3568 within the SHARP repression domain, enhancing SHARP-mediated repression of Notch target genes. Yeast two-hybrid, co-immunoprecipitation, phosphorylation site mapping, dominant-negative Pak1 and siRNA, reporter assays Oncogene Medium 15824732
2015 SHARP (SPEN) directly interacts with Xist lncRNA and is required for Xist-mediated transcriptional silencing of the inactive X chromosome, exclusion of RNA polymerase II, and recruitment of PRC2. SHARP interacts with the SMRT corepressor, which activates HDAC3, and both SMRT and HDAC3 are required for silencing. RNA antisense purification with quantitative mass spectrometry (RAP-MS), shRNA knockdown, Pol II ChIP, PRC2 ChIP Nature High 25915022
2015 Spen is genetically required for gene repression by Xist RNA in X chromosome inactivation, identified through forward genetic screening in haploid mouse ESCs. Spen loss did not affect Xist RNA localization or recruitment of Polycomb protein Ezh2. Forward genetic screen in haploid ESCs, gene deletion, Xist RNA FISH, Ezh2 ChIP Cell reports High 26190100
2015 Spen (RBM15 and Wtap) is required for Xist RNA-mediated silencing; Spen co-localizes with Xist RNA within the nuclear matrix subcompartment as shown by super-resolution 3D-SIM microscopy. Pooled shRNA screen, super-resolution 3D-SIM microscopy, RNA FISH co-localization Cell reports High 26190105
2015 SPEN functions as a tumor suppressor in ERα-positive breast cancer cells; SPEN binds ERα in a ligand-independent manner and negatively regulates transcription of ERα target genes. SPEN overexpression sensitizes cells to tamoxifen-induced apoptosis. Co-immunoprecipitation, functional assays (proliferation, tumor growth), microarray pathway analysis, in vitro and in vivo models Cancer research Medium 26297734
2017 SPEN regulates primary cilia formation and cell migration in breast cancer cells; SPEN knockdown decreased primary cilia levels, and KIF3A silencing (a ciliogenic factor) partially reversed SPEN's effects on migration, suggesting SPEN coordinates cellular movement through primary cilia-dependent mechanisms. shRNA knockdown, immunofluorescence for primary cilia, cell migration assays, epistasis with KIF3A Breast cancer research Medium 28877752
2019 Crystal structure of RBPJ bound to SHARP (SPEN) and DNA revealed the mode of SHARP binding to RBPJ; structure-based RBPJ mutants deficient for SHARP binding were incapable of repressing Notch-responsive transcription in cells. X-ray crystallography, isothermal titration calorimetry, structure-based mutagenesis, transcriptional reporter assays in cells Cell reports High 30673607
2020 SPEN is essential for initiating gene silencing on the X chromosome in preimplantation embryos and ESCs; it is immediately recruited to the X chromosome upon Xist upregulation and targeted to enhancers and promoters of active genes. The SPOC domain is a major effector of gene-silencing, and tethering SPOC to Xist RNA is sufficient to mediate silencing. SPEN's protein partners include NCoR/SMRT, the m6A RNA methylation machinery, NuRD complex, RNA Pol II, and transcription initiation/elongation factors. Mouse genetic knockouts (preimplantation embryos and ESCs), ChIP-seq, RNA-seq, SPOC domain tethering experiments, mass spectrometry proteomics of SPOC partners Nature High 32025035
2020 Spen binds to endogenous retroviral (ERV) RNAs that show structural similarity to the A-repeat of Xist through its RRM domains; ERV RNA and Xist A-repeat compete for Spen RRM binding. Loss of Spen activates ERV elements with gain of chromatin accessibility and active histone modifications. Insertion of an ERV into A-repeat-deficient Xist rescues Spen binding and local gene silencing. CLIP-seq, RRM domain binding assays, ATAC-seq, ChIP-seq, Spen KO ESCs, ERV insertion into Xist transgene eLife High 32379046
2021 SPEN is required for Xist upregulation during initiation of X chromosome inactivation; Spen null female ESCs are defective in Xist upregulation upon differentiation. SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation, and failed Xist upregulation in Spen-/- ESCs can be rescued by concomitant removal of Tsix. Spen null mouse ESCs, RNA FISH, genetic epistasis (Tsix deletion rescue), differentiation assays Nature communications High 34853312
2022 Xist drives non-stoichiometric recruitment of SHARP/SPEN to amplify its abundance across the inactive X through concentration-dependent homotypic assemblies of SHARP. This spatial amplification is required for chromosome-wide silencing. Xist also suppresses production of its own RNA through SHARP, constraining Xist levels and restricting its spread beyond the X. Single-molecule RNA FISH, protein imaging, SHARP domain mutants, Xist expression level manipulation, ChIP-seq Nature structural & molecular biology High 35301492
2022 SPEN and Polycomb pathways function in parallel (not sequentially) to establish X-linked gene silencing; a SPEN separation-of-function mutation showed that SPEN also has a role in correct localization of Xist RNA in cis. Differentiation-dependent recruitment of SmcHD1 is additionally required for silencing many X-linked genes. SPEN separation-of-function mutation, Xist RNA FISH, RNA-seq in differentiating ESCs, SmcHD1 ChIP/genetic analysis Cell reports High 35584662
2011 MINT (SPEN) forms a high-affinity complex with CSL (RBPJ) in the Notch pathway; isothermal titration calorimetry defined the domains of MINT and CSL necessary and sufficient for complex formation, and the MINT-binding region of CSL inhibited Notch signaling in transcriptional reporter assays. Isothermal titration calorimetry, domain deletion analysis, transcriptional reporter assays The Journal of biological chemistry High 21372128
2024 XIST triggers deposition of polycomb-mediated repressive histone modifications and dampens transcription of most X-linked genes in a SPEN-dependent manner during human preimplantation development, demonstrating SPEN is required for both XCI and X chromosome transcriptional dampening. Naive human ESC knockouts, ChIP-seq (H3K27me3), RNA-seq, genetic epistasis Nature structural & molecular biology High 38834912

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature 898 25915022
2020 Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19. Cell 462 33171100
1992 SRY, like HMG1, recognizes sharp angles in DNA. The EMBO journal 401 1425584
2020 The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice. Nature communications 368 33177522
1992 Membrane properties of dentate gyrus granule cells: comparison of sharp microelectrode and whole-cell recordings. Journal of neurophysiology 296 1597717
2001 Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes & development 277 11331609
2004 Spontaneous sharp bending of double-stranded DNA. Molecular cell 256 15125838
2002 SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. The EMBO journal 231 12374742
2015 A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing. Cell reports 227 26190105
2003 Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity 220 12594956
2015 Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells. Cell reports 200 26190100
2014 Mechanisms of sharp wave initiation and ripple generation. The Journal of neuroscience : the official journal of the Society for Neuroscience 197 25143618
2015 Determinants of different deep and superficial CA1 pyramidal cell dynamics during sharp-wave ripples. Nature neuroscience 187 26214372
2001 Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America 187 11344311
2000 Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges. Journal of cataract and refractive surgery 176 11033405
2020 SPEN integrates transcriptional and epigenetic control of X-inactivation. Nature 160 32025035
2005 RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. Molecular and cellular biology 150 16287852
2009 Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4). European journal of human genetics : EJHG 145 19172991
2003 A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. Genes & development 134 12897056
2013 Specified neural progenitors sort to form sharp domains after noisy Shh signaling. Cell 133 23622240
2011 Sharp Ca²⁺ nanodomains beneath the ribbon promote highly synchronous multivesicular release at hair cell synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 132 22090491
2003 Salvinorin A: the "magic mint" hallucinogen finds a molecular target in the kappa opioid receptor. Trends in pharmacological sciences 119 12628350
2002 Regulation of APP-dependent transcription complexes by Mint/X11s: differential functions of Mint isoforms. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 12196555
2017 Mechanisms for Selective Single-Cell Reactivation during Offline Sharp-Wave Ripples and Their Distortion by Fast Ripples. Neuron 89 28641116
2022 Xist spatially amplifies SHARP/SPEN recruitment to balance chromosome-wide silencing and specificity to the X chromosome. Nature structural & molecular biology 87 35301492
1994 HMG domain proteins induce sharp bends in cisplatin-modified DNA. Biochemistry 86 7999772
1999 The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter. Biochemistry 83 10451362
2021 Cholinergic suppression of hippocampal sharp-wave ripples impairs working memory. Proceedings of the National Academy of Sciences of the United States of America 79 33833054
2014 Physiological sharp wave-ripples and interictal events in vitro: what's the difference? Brain : a journal of neurology 76 24390441
1999 spen encodes an RNP motif protein that interacts with Hox pathways to repress the development of head-like sclerites in the Drosophila trunk. Development (Cambridge, England) 76 10556062
2018 A novel pyramidal cell type promotes sharp-wave synchronization in the hippocampus. Nature neuroscience 75 29915194
2016 Coordinated Interaction between Hippocampal Sharp-Wave Ripples and Anterior Cingulate Unit Activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 73 27733616
2021 SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females. American journal of human genetics 72 33596411
2017 MINT: a multivariate integrative method to identify reproducible molecular signatures across independent experiments and platforms. BMC bioinformatics 69 28241739
2006 The X11/Mint family of adaptor proteins. Brain research reviews 69 16764936
2008 Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 19118172
2016 Draft Genome Sequence of Mentha longifolia and Development of Resources for Mint Cultivar Improvement. Molecular plant 62 27867107
2010 Targeting GSK-3 family members in the heart: a very sharp double-edged sword. Journal of molecular and cellular cardiology 62 21163265
2018 A database-driven approach identifies additional diterpene synthase activities in the mint family (Lamiaceae). The Journal of biological chemistry 56 30498089
2020 Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation. eLife 51 32379046
2019 Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity. eLife 50 31223115
2021 Widespread premature transcription termination of Arabidopsis thaliana NLR genes by the spen protein FPA. eLife 48 33904405
2015 The Estrogen Receptor Cofactor SPEN Functions as a Tumor Suppressor and Candidate Biomarker of Drug Responsiveness in Hormone-Dependent Breast Cancers. Cancer research 47 26297734
2011 Transcriptional repression in the Notch pathway: thermodynamic characterization of CSL-MINT (Msx2-interacting nuclear target protein) complexes. The Journal of biological chemistry 45 21372128
2022 Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice. eLife 43 35411847
2010 Neuroprotective and neurochemical properties of mint extracts. Phytotherapy research : PTR 43 19943334
2017 Disruption of perineuronal nets increases the frequency of sharp wave ripple events. Hippocampus 42 28921856
2019 Structural and Functional Studies of the RBPJ-SHARP Complex Reveal a Conserved Corepressor Binding Site. Cell reports 40 30673607
2017 SPEN, a new player in primary cilia formation and cell migration in breast cancer. Breast cancer research : BCR 40 28877752
2012 G9a mediates Sharp-1-dependent inhibition of skeletal muscle differentiation. Molecular biology of the cell 40 23087213
2005 An essential role of Pak1 phosphorylation of SHARP in Notch signaling. Oncogene 38 15824732
2014 Mint proteins are required for synaptic activity-dependent amyloid precursor protein (APP) trafficking and amyloid β generation. The Journal of biological chemistry 37 24742670
2021 SPEN is required for Xist upregulation during initiation of X chromosome inactivation. Nature communications 35 34853312
2019 Cell lysis via acoustically oscillating sharp edges. Lab on a chip 35 31720640
2021 Sharp Increase of Problematic Mitogenomes of Birds: Causes, Consequences, and Remedies. Genome biology and evolution 34 34505894
2014 Stra13 and Sharp-1, the non-grouchy regulators of development and disease. Current topics in developmental biology 33 25248481
2013 Sharp wave/ripple network oscillations and learning-associated hippocampal maps. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 33 24366138
2012 Muscarinic receptor activation disrupts hippocampal sharp wave-ripples. Brain research 33 22608077
2010 Radioprotective potential of mint: a brief review. Journal of cancer research and therapeutics 33 21119249
2023 Inhibitory control of sharp-wave ripple duration during learning in hippocampal recurrent networks. Nature neuroscience 32 37081295
2019 Intracellular Photothermal Delivery for Suspension Cells Using Sharp Nanoscale Tips in Microwells. ACS nano 32 31487464
2009 The hypoxia-regulated transcription factor DEC1 (Stra13, SHARP-2) and its expression in gastric cancer. Omics : a journal of integrative biology 31 19624270
2022 Reorganization of CA1 dendritic dynamics by hippocampal sharp-wave ripples during learning. Neuron 30 35041805
2022 Rationale and design for the myocardial ischemia and transfusion (MINT) randomized clinical trial. American heart journal 30 36417955
2016 The wheat calcium-dependent protein kinase TaCPK7-D positively regulates host resistance to sharp eyespot disease. Molecular plant pathology 30 26720854
2020 Current Perspectives on Characteristics, Compositions, and Toxicological Effects of E-Cigarettes Containing Tobacco and Menthol/Mint Flavors. Frontiers in physiology 29 33329065
2022 User-friendly microfluidic manufacturing of hydrogel microspheres with sharp needle. Biofabrication 28 35193129
2021 Overexpression of TaSTT3b-2B improves resistance to sharp eyespot and increases grain weight in wheat. Plant biotechnology journal 27 34873799
2020 Generation of Sharp Wave-Ripple Events by Disinhibition. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 32913107
2020 SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma. Cell death & disease 26 32641685
2015 MINT: software to identify motifs and short-range interactions in trajectories of nucleic acids. Nucleic acids research 26 26024667
2007 Sharp melting in DNA-linked nanostructure systems: thermodynamic models of DNA-linked polymers. The journal of physical chemistry. B 26 17616117
2001 Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1 x Stra13 x SHARP-2/BHLHB2. Journal of biochemistry 26 11226878
2022 Surfaces Containing Sharp Nanostructures Enhance Antibiotic Efficacy. Nano letters 25 35900125
2021 Subiculum as a generator of sharp wave-ripples in the rodent hippocampus. Cell reports 24 33882307
2020 Potential factors influencing replay across CA1 during sharp-wave ripples. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 24 32248778
2009 Need for sharp phenotypes in QTL detection for calving traits in dairy cattle. Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 24 19912419
2022 Xist-mediated silencing requires additive functions of SPEN and Polycomb together with differentiation-dependent recruitment of SmcHD1. Cell reports 23 35584662
2020 Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity. Scientific reports 23 33208773
2022 Polyphenol Contents, Potential Antioxidant, Anticholinergic and Antidiabetic Properties of Mountain Mint (Cyclotrichium leucotrichum). Chemistry & biodiversity 22 35015378
2020 Characteristics and upregulation of antioxidant enzymes of kitchen mint and oolong tea kombucha beverages. Journal of food biochemistry 22 33249612
2017 A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres. eLife 22 28826474
2023 Two coral fluorescent proteins of distinct colors for sharp visualization of cell-cycle progression. Cell structure and function 21 37394513
2020 Using the MINT Database to Search Protein Interactions. Current protocols in bioinformatics 21 31945268
2020 DNA6mA-MINT: DNA-6mA Modification Identification Neural Tool. Genes 20 32764497
2022 Cell-type-specific silence in thalamocortical circuits precedes hippocampal sharp-wave ripples. Cell reports 19 35905724
2022 Nanotechnology-integrated ferroptosis inducers: a sharp sword against tumor drug resistance. Journal of materials chemistry. B 19 36043505
2023 A cell wall invertase modulates resistance to fusarium crown rot and sharp eyespot in common wheat. Journal of integrative plant biology 18 36912577
2019 Anti-Photoaging Effect of Korean Mint (Agastache rugosa Kuntze) Extract on UVB-Irradiated Human Dermal Fibroblasts. Preventive nutrition and food science 18 31915640
2024 XIST dampens X chromosome activity in a SPEN-dependent manner during early human development. Nature structural & molecular biology 17 38834912
2013 Sharp-1 regulates TGF-β signaling and skeletal muscle regeneration. Journal of cell science 17 24357723
2024 Immunogenic cell death-based oncolytic virus therapy: A sharp sword of tumor immunotherapy. European journal of pharmacology 16 39154830
2017 An autonomous metabolic role for Spen. PLoS genetics 16 28640815
2015 Spen is required for pigment cell survival during pupal development in Drosophila. Developmental biology 16 25872184
2021 TaWAK2A-800, a Wall-Associated Kinase, Participates Positively in Resistance to Fusarium Head Blight and Sharp Eyespot in Wheat. International journal of molecular sciences 15 34768923
2020 Gene-Diet Interactions: Dietary Rescue of Metabolic Effects in spen-Depleted Drosophila melanogaster. Genetics 15 32107279
2020 Elements at the 5' end of Xist harbor SPEN-independent transcriptional antiterminator activity. Nucleic acids research 15 32986830
2020 Cellular Base of Mint Allelopathy: Menthone Affects Plant Microtubules. Frontiers in plant science 15 33042176
2019 Impairment of Sharp-Wave Ripples in a Murine Model of Dravet Syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 15 31537705
2005 Mint represses transactivation of the type II collagen gene enhancer through interaction with alpha A-crystallin-binding protein 1. The Journal of biological chemistry 15 15778499