Affinage

TLE4

Transducin-like enhancer protein 4 · UniProt Q04727

Round 2 corrected
Length
773 aa
Mass
83.8 kDa
Annotated
2026-04-28
130 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TLE4 is a nuclear transcriptional corepressor of the Groucho/TLE family that is recruited to target gene promoters by diverse DNA-binding transcription factors—including TCF/LEF, Pax5, PU.1, FoxD3, Cux1, and SoxE proteins—through conserved interaction motifs such as the eh1/GEH and octapeptide domains (PMID:10811620, PMID:17138566, PMID:11266540). TLE4 mediates transcriptional repression by recruiting histone deacetylases HDAC1 and HDAC3 to target promoters, as demonstrated at the p27kip1 locus in developing kidney (PMID:11266540, PMID:19332113). The corepressor activity of TLE4 is regulated by post-translational modifications of its binding partners, exemplified by SUMOylation of SoxE factors that switches them from activators to TLE4-recruiting repressors (PMID:22927467). In vivo, TLE4 controls tectal patterning, neuronal laminar migration, B-cell gene regulation, and mesoderm induction (PMID:10772799, PMID:12490552, PMID:14993928, PMID:17138566).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1992 Medium

    Identification of TLE4 as a nuclear protein homologous to Drosophila Groucho established it as a member of a conserved family of candidate transcriptional regulators, opening the question of what transcription factors recruit it and how it mediates repression.

    Evidence cDNA cloning, sequence homology, and immunostaining for nuclear localization in human tissues

    PMID:1303260

    Open questions at the time
    • No transcription factor partners or repression mechanism identified at this stage
    • Expression data descriptive, no functional assay performed
  2. 2000 High

    Demonstration that Pax5 recruits TLE4/Grg4 via its octapeptide motif and that TLE4 represses Pax5 target genes answered the question of how a sequence-specific transcription factor physically engages a Groucho-family corepressor, defining the domain architecture underlying this interaction.

    Evidence Yeast two-hybrid, reciprocal Co-IP, transcriptional reporter assays, domain mapping, and in vivo phosphorylation analysis

    PMID:10811620

    Open questions at the time
    • Chromatin-level mechanism of repression not yet defined
    • Whether HDAC recruitment is involved was untested at this point
  3. 2000 Medium

    In vivo overexpression and dominant-negative studies in chick tectum showed that TLE4/Grg4 antagonizes tectum-organizer gene expression (En-2, Pax5, Fgf8), establishing TLE4 as a functionally important repressor in neural patterning.

    Evidence In ovo electroporation gain- and dominant-negative loss-of-function with in situ hybridization readouts in chick embryos

    PMID:10772799

    Open questions at the time
    • Direct transcriptional targets versus indirect effects not distinguished
    • Single model organism
  4. 2001 High

    Showing that all long TLE proteins including TLE4 physically interact with TCF/LEF factors and recruit HDAC1 to mediate repression resolved how Groucho-family corepressors mechanistically silence Wnt target genes, distinguishing full-length TLEs from the short de-repressor Grg5.

    Evidence Co-immunoprecipitation and luciferase reporter assays testing multiple TCF/TLE combinations with HDAC binding assays

    PMID:11266540

    Open questions at the time
    • Whether HDAC catalytic activity is strictly required for repression not tested with deacetylase-dead mutants
    • Genomic targets of TCF/TLE4 complexes not mapped
  5. 2003 Medium

    Reciprocal gain- and loss-of-function experiments revealed that TLE4/Grg4 directly controls postmitotic neuronal migration and laminar positioning in the optic tectum, extending its role beyond transcriptional target gene regulation to cellular migratory behavior.

    Evidence Clonal electroporation, morpholino knockdown, and dominant-negative overexpression in chick tectum with histological laminar analysis

    PMID:12490552

    Open questions at the time
    • Downstream transcriptional targets mediating migration not identified
    • Mechanism linking repression to cell migration unknown
  6. 2004 Medium

    Co-recruitment of TLE4/Grg4 by PU.1 together with Pax5 at the IgH enhancer, and the observation that Grg4 protein decreases upon B-cell activation, revealed temporal regulation of TLE4 corepressor availability as a mechanism for controlling B-lineage gene expression.

    Evidence Co-immunoprecipitation, luciferase reporter assays, and western blotting in B-cell lines before and after activation

    PMID:14993928

    Open questions at the time
    • Mechanism of Grg4 protein downregulation (proteasomal, transcriptional) not defined
    • Genome-wide B-cell targets of PU.1/TLE4 complex unknown
  7. 2006 High

    Mutagenesis of the FoxD3 eh1/GEH motif abolished both TLE4/Grg4 binding and FoxD3-mediated repression and mesoderm induction, providing the first direct evidence that a single short motif is necessary and sufficient for Groucho recruitment and in vivo developmental function.

    Evidence Co-IP with point mutants, transcriptional reporter assays, and Xenopus embryo injection with rescue experiments

    PMID:17138566

    Open questions at the time
    • Structural basis of eh1–TLE4 interaction not resolved at atomic level
    • Whether all eh1-containing factors use identical TLE4 surfaces is unknown
  8. 2009 High

    ChIP demonstration that Cux1, TLE4/Grg4, HDAC1, and HDAC3 co-occupy two sites on the p27kip1 promoter in neonatal kidney established that TLE4 functions as a chromatin-associated corepressor complex with multiple HDACs at an endogenous locus relevant to kidney development.

    Evidence Chromatin immunoprecipitation in neonatal mouse kidney, Co-IP, luciferase reporter, DNase I footprinting

    PMID:19332113

    Open questions at the time
    • Whether HDAC1 and HDAC3 have redundant or distinct roles in this complex untested
    • Genome-wide binding profile of TLE4 in kidney not available
  9. 2012 High

    Discovering that SUMOylation of SoxE factors switches them from CBP/p300-associated activators to TLE4/Grg4-recruiting repressors resolved how a single transcription factor toggles between activation and repression, revealing post-translational modification of the partner as a regulatory input for TLE4 recruitment.

    Evidence Co-IP, SUMO modification assays, and functional reporter assays in Xenopus embryos with SUMOylation-site mutants

    PMID:22927467

    Open questions at the time
    • Whether other TLE4-interacting factors are similarly regulated by SUMOylation is untested
    • Structural basis for SUMO-dependent differential binding not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the genome-wide binding landscape of TLE4 in any mammalian cell type, the structural basis of TLE4's WD40 and Q-domain interactions with diverse transcription factors, and whether TLE4 has non-redundant functions distinct from other long TLE family members in vivo.
  • No genome-wide ChIP-seq or CUT&RUN map for TLE4 reported
  • No crystal or cryo-EM structure of TLE4 in complex with a transcription factor
  • Genetic knockout studies distinguishing TLE4 from TLE1/2/3 in mammals are lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 3 GO:0005654 nucleoplasm 2 R-HSA-162582 Signal Transduction 2 R-HSA-4839726 Chromatin organization 2
Partners
CUX1FOXD3HDAC1HDAC3PAX5SPI1TCF7L2

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Human TLE proteins (including TLE4) were identified as nuclear proteins homologous to Drosophila Groucho/E(spl) m9/10, establishing TLE4 as a member of a conserved family of nuclear corepressors differentially expressed in human tissues. cDNA cloning, sequence homology analysis, nuclear localization by immunostaining Nature genetics Medium 1303260
2001 All mammalian Groucho/TLE family members (including TLE4/Grg4) physically interact with TCF/LEF transcription factors and repress TCF-mediated transcriptional activation; long TLE proteins (including TLE4) interact with histone deacetylase HDAC1 to mediate repression, whereas the short family member Grg5 acts as a de-repressor by failing to recruit HDAC. Co-immunoprecipitation, reporter/luciferase transcriptional assays, HDAC binding assays in cell lines Nucleic acids research High 11266540
2000 Pax5 (BSAP) recruits Grg4 (TLE4 ortholog) as a transcriptional corepressor via two separate interaction domains: the N-terminal Q and central SP regions of Grg4, and the octapeptide motif and C-terminal transactivation domain of Pax5; this interaction represses Pax5 target genes and alters the phosphorylation state of Grg4 in vivo. Yeast two-hybrid screen, co-immunoprecipitation, transcriptional reporter assays, in vivo phosphorylation analysis The EMBO journal High 10811620
2004 Grg4 (TLE4 ortholog) is co-recruited by PU.1 in B-lineage cells; PU.1 physically interacts with Grg4 and, in conjunction with Pax5, represses IgH enhancer activity in a position-dependent manner; Grg4 protein levels decrease following B-cell activation, suggesting temporal regulation of this corepressor. Co-immunoprecipitation, luciferase reporter assays, western blotting for Grg4 levels in activated B cells EMBO reports Medium 14993928
2006 FoxD3 physically interacts with Grg4 (TLE4 ortholog) via an eh1/GEH Groucho-interaction motif in its C-terminal domain; this interaction is required for FoxD3-mediated transcriptional repression and mesoderm induction in Xenopus. Deletion or point mutagenesis of the eh1 motif abolishes both Grg4 binding and FoxD3 repression activity; the dominant-inhibitory Grg5 antagonizes this function. Co-immunoprecipitation, deletion/point mutagenesis, transcriptional reporter assays, Xenopus embryo injection with rescue The Journal of biological chemistry High 17138566
2009 The homeodomain protein Cux1 directly interacts with Grg4 (TLE4 ortholog) in developing kidney; Grg4 enhances Cux1-mediated repression of the p27kip1 promoter. ChIP assays demonstrated that Cux1, Grg4, HDAC1, and HDAC3 are co-recruited to two separate sites in the p27kip1 promoter in vivo in neonatal kidney tissue. Co-immunoprecipitation, luciferase reporter assay, chromatin immunoprecipitation (ChIP), DNase I footprinting Gene High 19332113
2012 SUMOylation of SoxE transcription factors promotes their recruitment of Grg4 (TLE4 ortholog) as a corepressor while displacing coactivators CBP/p300; this SUMO-dependent switch converts SoxE from a transcriptional activator to a repressor in Xenopus neural crest development, demonstrating that TLE4/Grg4 recruitment is regulated by post-translational modification of its binding partner. Co-immunoprecipitation, SUMO modification assays, transcriptional reporter assays in Xenopus embryos The Journal of cell biology High 22927467
2000 Chick Grg4 (TLE4 ortholog) functions as a transcriptional repressor that antagonizes tectum-organizing activity in the mesencephalon; Grg4 overexpression by in ovo electroporation repressed En-2, Pax5, Fgf8, and EphrinA2 expression while upregulating Pax6, and co-transfection with Pax5 canceled tectum-inducing activity of Pax5. The N-terminal domain of Grg4 acted as a dominant negative and induced En-2 expression, confirming nuclear repressive function. In ovo electroporation (gain- and dominant-negative loss-of-function), immunostaining, in situ hybridization Developmental biology Medium 10772799
2003 Grg4 (TLE4 ortholog) directs tectal postmitotic cell migration to specific laminae in the chick optic tectum; clonal misexpression of Grg4 caused cells to migrate to laminae h–j of the SGFS, whereas morpholino knockdown or dominant-negative Grg4 produced the opposite effect, demonstrating a direct role in controlling neuronal migration and laminar positioning. Clonal electroporation overexpression, morpholino antisense knockdown, dominant-negative overexpression, histological analysis of laminar position Development (Cambridge, England) Medium 12490552
2014 PAX2 mutations associated with adult-onset FSGS alter PAX2 interaction with repressor proteins (including Grg/TLE family members), resulting in enhanced repressor activity; in vitro functional studies showed that specific PAX2 FSGS-associated mutations perturb interaction with TLE corepressors. In vitro interaction/functional assays, in silico structural modeling, transactivation assays Journal of the American Society of Nephrology Low 24676634
2015 Large-scale affinity-purification mass spectrometry (BioPlex) identified TLE4 as part of protein interaction communities in HEK293T cells, placing TLE4 within defined protein complexes in the human interactome. Affinity purification mass spectrometry (AP-MS) at proteome scale Cell Low 26186194
2004 Large-scale phosphoproteomic analysis of HeLa cell nuclear proteins identified phosphorylation sites on TLE4, indicating that TLE4 undergoes nuclear phosphorylation in human cells. Strong cation exchange chromatography enrichment of phosphopeptides, tandem MS Proceedings of the National Academy of Sciences of the United States of America Low 15302935

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cell 1757 28988769
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2003 HES and HERP families: multiple effectors of the Notch signaling pathway. Journal of cellular physiology 1015 12548545
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2014 Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nature genetics 834 24509480
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1992 Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes & development 597 1340473
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
1995 Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. Genes & development 505 7590239
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1995 The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling. Genes & development 388 7590238
2020 CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal transduction and targeted therapy 366 33361760
2001 All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic acids research 310 11266540
1996 Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signalling in Drosophila. Development (Cambridge, England) 302 8565827
1992 Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. Nature genetics 286 1303260
1989 Closely related transcripts encoded by the neurogenic gene complex enhancer of split of Drosophila melanogaster. The EMBO journal 267 2540957
2003 Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea. Journal of the Association for Research in Otolaryngology : JARO 231 14690052
1999 Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Nature 214 10028969
2000 Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family. The EMBO journal 211 10811620
1992 The Enhancer of split [E(spl)] locus of Drosophila encodes seven independent helix-loop-helix proteins. Proceedings of the National Academy of Sciences of the United States of America 187 1528887
2001 HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling. Molecular and cellular biology 185 11486045
1998 The function of hairy-related bHLH repressor proteins in cell fate decisions. BioEssays : news and reviews in molecular, cellular and developmental biology 182 9619101
2019 Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling. Nature communications 178 31278255
2014 Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium. Circulation. Cardiovascular genetics 175 24823311
2013 The protein interaction landscape of the human CMGC kinase group. Cell reports 174 23602568
2004 Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain. Development (Cambridge, England) 174 15105370
1997 Notch signalling regulates veinlet expression and establishes boundaries between veins and interveins in the Drosophila wing. Development (Cambridge, England) 166 9169839
1999 her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is a target of NOTCH signalling. Development (Cambridge, England) 160 10101116
1987 The embryonic expression of the Notch locus of Drosophila melanogaster and the implications of point mutations in the extracellular EGF-like domain of the predicted protein. The EMBO journal 155 3123218
1996 Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye. Current biology : CB 150 8939576
2002 An EGFR/Ebi/Sno pathway promotes delta expression by inactivating Su(H)/SMRTER repression during inductive notch signaling. Cell 147 12230979
2010 Transcriptional control of stem cell maintenance in the Drosophila intestine. Development (Cambridge, England) 146 20147375
2001 Novel Notch alleles reveal a Deltex-dependent pathway repressing neural fate. Current biology : CB 139 11719214
2009 Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing. Molecular cell 135 19782028
1988 The molecular genetics of Enhancer of split, a gene required for embryonic neural development in Drosophila. The EMBO journal 134 3145200
2004 A Notch feeling of somite segmentation and beyond. Developmental biology 131 14697349
2014 Progressive regulation of sesquiterpene biosynthesis in Arabidopsis and Patchouli (Pogostemon cablin) by the miR156-targeted SPL transcription factors. Molecular plant 129 25578275
2010 Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms. Diabetes care 129 20889853
1997 The metalloprotease-disintegrin Kuzbanian participates in Notch activation during growth and patterning of Drosophila imaginal discs. Development (Cambridge, England) 128 9428413
1999 her1, a zebrafish pair-rule like gene, acts downstream of notch signalling to control somite development. Development (Cambridge, England) 124 10357943
2022 Human transcription factor protein interaction networks. Nature communications 123 35140242
1999 Identification and expression of a novel family of bHLH cDNAs related to Drosophila hairy and enhancer of split. Biochemical and biophysical research communications 122 10403790
2015 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. Molecular systems biology 120 25609649
2009 Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children. PLoS genetics 119 19714205
2011 Proteomic characterization of the human sperm nucleus. Proteomics 116 21630459
2010 Analyses of shared genetic factors between asthma and obesity in children. The Journal of allergy and clinical immunology 111 20816195
1999 Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA research : an international journal for rapid publication of reports on genes and genomes 111 10574462
1998 Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of Drosophila hairy and Enhancer of split. Genomics 108 9570950
1999 Several levels of EGF receptor signaling during photoreceptor specification in wild-type, Ellipse, and null mutant Drosophila. Developmental biology 107 9882502
1987 Cell autonomy of expression of neurogenic genes of Drosophila melanogaster. Proceedings of the National Academy of Sciences of the United States of America 106 3110768
1992 Enhancer of splitD, a dominant mutation of Drosophila, and its use in the study of functional domains of a helix-loop-helix protein. Proceedings of the National Academy of Sciences of the United States of America 103 1631102
2004 The vertebrate segmentation clock. Current opinion in genetics & development 100 15261657
2014 Mutations in PAX2 associate with adult-onset FSGS. Journal of the American Society of Nephrology : JASN 94 24676634
2009 Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins. PloS one 94 19587787
1993 Identification of esg, a genetic locus involved in cell-cell signaling during Myxococcus xanthus development. Journal of bacteriology 93 8253664
2012 Charting the landscape of tandem BRCT domain-mediated protein interactions. Science signaling 92 22990118
2000 The enhancer of split complex of Drosophila includes four Notch-regulated members of the bearded gene family. Development (Cambridge, England) 91 10903170
2001 HERP1 is a cell type-specific primary target of Notch. The Journal of biological chemistry 87 11741889
2015 Quantitative interaction proteomics of neurodegenerative disease proteins. Cell reports 86 25959826
2004 DNA sequence and analysis of human chromosome 9. Nature 86 15164053
1987 The enhancer of split locus and neurogenesis in Drosophila melanogaster. Developmental biology 86 3109981
1993 Molecular characterization of HES-2, a mammalian helix-loop-helix factor structurally related to Drosophila hairy and Enhancer of split. European journal of biochemistry 83 8354270
2001 The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 11160397
2021 SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies. medRxiv : the preprint server for health sciences 77 33619509
2014 Multiple functions of the SNARE protein Snap29 in autophagy, endocytic, and exocytic trafficking during epithelial formation in Drosophila. Autophagy 76 25551675
1994 Neuroectodermal transcription of the Drosophila neurogenic genes E(spl) and HLH-m5 is regulated by proneural genes. Development (Cambridge, England) 75 7600959
2013 The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors. Genes & development 74 23468431
1996 Transcripts of Grg4, a murine groucho-related gene, are detected in adjacent tissues to other murine neurogenic gene homologues during embryonic development. Mechanisms of development 71 8892234
1997 The Drosophila gene Bearded encodes a novel small protein and shares 3' UTR sequence motifs with multiple Enhancer of split complex genes. Development (Cambridge, England) 68 9374401
2003 Two modes of recruitment of E(spl) repressors onto target genes. Development (Cambridge, England) 66 12466194
2009 The SPOROCYTELESS/NOZZLE gene is involved in controlling stamen identity in Arabidopsis. Plant physiology 63 19726570
2000 Antagonism of notch signaling activity by members of a novel protein family encoded by the bearded and enhancer of split gene complexes. Development (Cambridge, England) 63 10603347
1995 The esg locus of Myxococcus xanthus encodes the E1 alpha and E1 beta subunits of a branched-chain keto acid dehydrogenase. Molecular microbiology 62 7565081
1997 Functional dissection of the Drosophila enhancer of split protein, a suppressor of neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 61 9177203
2008 Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 60 18358774
2012 bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation. Development (Cambridge, England) 59 22357926
2006 FoxD3 and Grg4 physically interact to repress transcription and induce mesoderm in Xenopus. The Journal of biological chemistry 57 17138566
2010 Notch signaling regulates neuroepithelial stem cell maintenance and neuroblast formation in Drosophila optic lobe development. Developmental biology 54 21146517
2016 Oxytocin receptor polymorphism and childhood social experiences shape adult personality, brain structure and neural correlates of mentalizing. NeuroImage 53 27109357
2011 Expression of hairy/enhancer of split genes in neural progenitors and neurogenesis domains of the adult zebrafish brain. The Journal of comparative neurology 53 21452233
2004 her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling. Development (Cambridge, England) 51 15169758
1995 Suppressor of hairless, the Drosophila homologue of RBP-J kappa, transactivates the neurogenic gene E(spl)m8. Idengaku zasshi 50 7546844
2012 Defining early human NK cell developmental stages in primary and secondary lymphoid tissues. PloS one 49 22319595
2004 Corecruitment of the Grg4 repressor by PU.1 is critical for Pax5-mediated repression of B-cell-specific genes. EMBO reports 49 14993928
1997 Synergy between suppressor of Hairless and Notch in regulation of Enhancer of split m gamma and m delta expression. Molecular and cellular biology 49 9271437
1995 Inhibition of cell fate in Drosophila by Enhancer of split genes. Mechanisms of development 49 7547476
2013 Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. PLoS genetics 46 23300480
2012 SUMOylated SoxE factors recruit Grg4 and function as transcriptional repressors in the neural crest. The Journal of cell biology 46 22927467
2024 CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis. Cancer discovery 42 38900051
2020 Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma. Proceedings of the National Academy of Sciences of the United States of America 40 33318203
2021 The Protease SplB of Staphylococcus aureus Targets Host Complement Components and Inhibits Complement-Mediated Bacterial Opsonophagocytosis. Journal of bacteriology 38 34633872
1998 Evidence for a novel Notch pathway required for muscle precursor selection in Drosophila. Mechanisms of development 38 10349619
2017 The Super Elongation Complex Drives Neural Stem Cell Fate Commitment. Developmental cell 36 28350987
2007 Identification of neural progenitor pools by E(Spl) factors in the embryonic and adult brain. Brain research bulletin 36 18331883
1993 Drosophila evolution challenges postulated redundancy in the E(spl) gene complex. Proceedings of the National Academy of Sciences of the United States of America 36 8516287
2000 Antagonizing activity of chick Grg4 against tectum-organizing activity. Developmental biology 35 10772799
1998 Design, characterization and anti-tumour cytotoxicity of a panel of recombinant, mammalian ribonuclease-based immunotoxins. British journal of cancer 35 9484808
2012 AMS-dependent and independent regulation of anther transcriptome and comparison with those affected by other Arabidopsis anther genes. BMC plant biology 34 22336428
2000 Coregulation of anterior and posterior mesendodermal development by a hairy-related transcriptional repressor. Genes & development 34 10887160
2000 Relationships between extramacrochaetae and Notch signalling in Drosophila wing development. Development (Cambridge, England) 33 10804180
2003 The role of Grg4 in tectal laminar formation. Development (Cambridge, England) 31 12490552
1997 A chimeric enhancer-of-split transcriptional activator drives neural development and achaete-scute expression. Molecular and cellular biology 31 9234693
2017 Identification of TPS family members in apple (Malus x domestica Borkh.) and the effect of sucrose sprays on TPS expression and floral induction. Plant physiology and biochemistry : PPB 30 28964942
2019 Endothelial surface glycocalyx (ESG) components and ultra-structure revealed by stochastic optical reconstruction microscopy (STORM). Biorheology 29 31045510
2016 Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling. PLoS genetics 29 27070787
1995 Protein characterization and targeted disruption of Grg, a mouse gene related to the groucho transcript of the Drosophila Enhancer of split complex. Developmental dynamics : an official publication of the American Association of Anatomists 29 8573724
2009 The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development. Gene 28 19332113
1997 Cloning and developmental expression of Xenopus cDNAs encoding the Enhancer of split groucho and related proteins. Gene 28 9300818
2001 Drosophila melanogaster casein kinase II interacts with and phosphorylates the basic helix-loop-helix proteins m5, m7, and m8 derived from the Enhancer of split complex. The Journal of biological chemistry 27 11208814
2021 Adenine base editing reduces misfolded protein accumulation and toxicity in alpha-1 antitrypsin deficient patient iPSC-hepatocytes. Molecular therapy : the journal of the American Society of Gene Therapy 26 34217893
2018 Characterization of Vv-miR156: Vv-SPL pairs involved in the modulation of grape berry development and ripening. Molecular genetics and genomics : MGG 26 29943289
2008 Molecular characterization and expression patterns of AMP deaminase1 (AMPD1) in porcine skeletal muscle. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 26 18638563
2002 A feel for the template: zinc finger protein transcription factors and chromatin. Biochemistry and cell biology = Biochimie et biologie cellulaire 26 12123285
1999 Notchspl is deficient for inductive processes in the eye, and E(spl)D enhances split by interfering with proneural activity. Developmental biology 25 10191054
2019 Regulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila. Nature communications 24 31375669
2014 E(spl): genetic, developmental, and evolutionary aspects of a group of invertebrate Hes proteins with close ties to Notch signaling. Current topics in developmental biology 24 25248478
2014 PFP/ESG: automated protein function prediction servers enhanced with Gene Ontology visualization tool. Bioinformatics (Oxford, England) 23 25273111
2004 Drosophila CK2 regulates eye morphogenesis via phosphorylation of E(spl)M8. Mechanisms of development 23 15003630
2019 MiR-3653 inhibits the metastasis and epithelial-mesenchymal transition of colon cancer by targeting Zeb2. Pathology, research and practice 21 31405759
2011 Zebrafish Her8a is activated by Su(H)-dependent Notch signaling and is essential for the inhibition of neurogenesis. PloS one 21 21541299
2010 Evolution of a genomic regulatory domain: the role of gene co-option and gene duplication in the Enhancer of split complex. Genome research 21 20458100
2004 Role of the Sc C terminus in transcriptional activation and E(spl) repressor recruitment. The Journal of biological chemistry 21 15507447
2003 Echinoid synergizes with the Notch signaling pathway in Drosophila mesothorax bristle patterning. Development (Cambridge, England) 21 14623820
1999 Overexpression of the m4 and malpha genes of the E(spl)-complex antagonizes notch mediated lateral inhibition. Mechanisms of development 20 10446264