Affinage

EPC1

Enhancer of polycomb homolog 1 · UniProt Q9H2F5

Length
836 aa
Mass
93.5 kDa
Annotated
2026-06-09
39 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPC1 (Enhancer of Polycomb 1) is a non-catalytic scaffolding subunit of the NuA4/TIP60 histone acetyltransferase complex that orients catalytic activity toward nucleosomal histones and couples it to specific chromatin outcomes (PMID:23109429, PMID:28108589). In the yeast Piccolo NuA4 ortholog Epl1, a short basic region within the conserved EPcA domain is positioned near the H2A tail, the H4 globular region, and nucleosomal DNA, and is required for nucleosomal H4/H2A acetyltransferase activity without being needed for nucleosome binding, while distinct Epl1 domains mediate subunit interaction, histone acetylation, and chromatin targeting — establishing that EPC1 promotes Esa1/TIP60 catalysis through structural scaffolding (PMID:23109429, PMID:28108589). A hydrophobic C-terminal fragment of EPC1 engages the MBT repeats of MBTD1 at a site distinct from the H4K20me-binding pocket, recruiting MBTD1 into the complex to influence transcription and DNA-repair pathway choice (PMID:32209463). Beyond its complex-assembly role, EPC1 acts in transcriptional control: it forms a proliferation-specific repressive complex with E2F6, DP1, EZH2, and Sin3B (PMID:15536069), and modulates E2F1 activity in a target-specific manner, activating anti-apoptotic genes (BCL-2, BIRC5) while suppressing genotoxin-induced apoptosis and supporting tumor cell motility (PMID:26350215). In hematopoiesis, EPC1 (with EPC2) is required for MLL-rearranged leukemia stem cell potential, acting upstream of MYC protein levels to prevent aberrant MYC accumulation (PMID:24166297), and sustains normal hematopoietic stem/progenitor proliferation by regulating H3 acetylation and DLST expression in cooperation with SRF and FOXR2 (PMID:38439957). EPC1 is also recruited with TIP60 by CCER1 nuclear condensates during spermiogenesis to drive H4 hyperacetylation needed for histone-to-protamine exchange (PMID:41670399).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2004 High

    Established EPC1 as a partner of transcriptional repressors, placing it in a proliferation-specific repressive complex rather than acting only as a generic acetyltransferase subunit.

    Evidence Yeast two-hybrid, in vitro binding, affinity purification/co-elution and cell-based repression assays defining an E2F6–DP1–EPC1–EZH2–Sin3B complex

    PMID:15536069

    Open questions at the time
    • Does not define which EPC1 region mediates these interactions
    • Repressed target genes not directly enumerated
    • Relationship to the NuA4/TIP60 complex not addressed
  2. 2012 High

    Defined the structural basis for how the EPcA domain promotes catalysis, showing the basic region orients the complex on the nucleosome for H4/H2A acetylation independent of nucleosome binding.

    Evidence In vitro reconstituted nucleosomal HAT assays with site-directed mutagenesis and site-specific cross-linking proximity mapping in yeast Piccolo NuA4 (Epl1 ortholog)

    PMID:23109429

    Open questions at the time
    • Demonstrated in yeast Epl1, not human EPC1 directly
    • Does not address full NuA4/TIP60 complex behavior
    • Atomic-resolution structure not obtained
  3. 2013 Medium

    Connected EPC1 to disease-relevant biology by placing it upstream of MYC protein levels in MLL-leukemia stem cells.

    Evidence shRNA knockdown screen, colony-forming and transplantation leukemia stem cell assays, transcriptional profiling, and pharmacological/genetic MYC epistasis in murine MLL-AF9 AML

    PMID:24166297

    Open questions at the time
    • Mechanism by which EPC1 limits MYC accumulation unresolved
    • Chromatin/acetylation events at MYC not mapped
    • Single-lab finding without orthogonal validation
  4. 2015 Medium

    Showed EPC1 modulates E2F1 transcriptional output to bias cells toward survival, linking it to apoptosis suppression and tumor cell motility.

    Evidence ChIP, co-IP, nuclear co-localization, siRNA knockdown with apoptosis/motility readouts and reporter assays

    PMID:26350215

    Open questions at the time
    • Whether NuA4/TIP60 acetyltransferase activity mediates target selectivity not shown
    • Direct vs indirect regulation of pro/anti-apoptotic targets not fully resolved
    • Single-lab study
  5. 2017 Medium

    Demonstrated genetically that EPC1/Epl1 is functionally interchangeable with the catalytic subunit in promoting acetylation, formalizing its scaffolding role through domain dissection.

    Evidence Genetic suppressor bypass screen (Rpd3L loss), deletion mapping, and in vivo histone acetylation and chromatin targeting assays in S. cerevisiae

    PMID:28108589

    Open questions at the time
    • Performed in yeast; human EPC1 domain assignments inferred
    • Specific subunit-binding interfaces not structurally resolved here
    • Single-lab study
  6. 2020 High

    Resolved how EPC1 recruits MBTD1 into NuA4/TIP60, providing a molecular handle linking complex composition to DNA-repair pathway choice.

    Evidence X-ray crystallography of the MBTD1–EPC1 complex with interface mutagenesis validated in cellular co-IP and DNA-repair readouts

    PMID:32209463

    Open questions at the time
    • Quantitative impact of MBTD1 recruitment on specific repair pathways not fully defined
    • Interplay with the E2F1/E2F6 functions of EPC1 unaddressed
  7. 2024 Medium

    Extended EPC1 function to normal hematopoietic stem/progenitor proliferation, identifying DLST as an H3-acetylation-regulated target.

    Evidence Morpholino/genetic knockdown in zebrafish, K562 knockdown, ChIP-based H3 acetylation and gene expression analysis with SRF/FOXR2 cooperation

    PMID:38439957

    Open questions at the time
    • Direct EPC1 occupancy at the DLST locus not shown
    • Mechanism of cooperation with SRF/FOXR2 unresolved
    • Single-lab study
  8. 2026 Medium

    Showed EPC1 is recruited by phase-separated CCER1 condensates with TIP60 to drive H4 hyperacetylation required for chromatin remodeling in spermiogenesis.

    Evidence IP-MS in CCER1-Tag knock-in mice, co-IP, H4 acetylation assays, and knock-in/knockout mouse phenotyping

    PMID:41670399

    Open questions at the time
    • Direct CCER1–EPC1 contact vs indirect recruitment not distinguished
    • Genomic targets of CCER1-directed acetylation not mapped
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EPC1's distinct activities — NuA4/TIP60 scaffolding, MBTD1 recruitment, E2F-family transcriptional regulation, and MYC restraint — are integrated within a single protein and coordinated across cell contexts remains unresolved.
  • No structural model of full-length human EPC1 within NuA4/TIP60
  • Whether E2F6/E2F1 regulation requires acetyltransferase activity unknown
  • Molecular link between EPC1 and MYC protein turnover undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 2 GO:0140110 transcription regulator activity 2 GO:0042393 histone binding 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0000228 nuclear chromosome 1 GO:0005634 nucleus 1
Pathway
R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-73894 DNA Repair 1
Partners
CCER1E2F1E2F6EPC2EZH2MBTD1SIN3BTFDP1
Complex memberships
E2F6–DP1–EPC1–EZH2–Sin3B repressive complexEP400 complexNuA4/TIP60 histone acetyltransferase complexPiccolo NuA4

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 EPC1 was identified as a binding partner of transcriptional repressor E2F6 via yeast two-hybrid screen; E2F6, DP1, and EPC1 form a stable core complex with repressive activity both in vitro and in vivo; EPC1 also interacts with the proliferation-specific polycomb protein EZH2, and affinity purification showed E2F6, DP1, EPC1, EZH2, and Sin3B co-elute as a novel complex that exists only in proliferating cells. Yeast two-hybrid screen, in vitro binding assay, affinity purification/co-elution, cell-based repression assay The Journal of biological chemistry High 15536069
2015 EPC1 physically interacts with E2F1 (E2F1 binds the EPC1 promoter; EPC1 co-localizes with E2F1 in the nucleus); depletion of EPC1 potentiates E2F1-mediated apoptosis after genotoxic treatment and abolishes tumor cell motility; EPC1 modulates E2F1 transcriptional activity in a target-gene-specific manner, activating anti-apoptotic genes (BCL-2, Survivin/BIRC5) and silencing pro-apoptotic targets. ChIP, co-immunoprecipitation, nuclear co-localization, siRNA knockdown with apoptosis and motility readouts, reporter/gene expression assays Nucleic acids research Medium 26350215
2013 EPC1 and EPC2, as components of the EP400 complex, are required for the clonogenic and leukemia stem cell potential of MLL-mutated AML cells; EPC1/EPC2 knockdown induces apoptosis in murine MLL-AF9 AML cells and causes MYC protein accumulation; pharmacological inhibition of MYC:MAX dimerization or concomitant MYC knockdown reduces apoptosis following EPC1 KD, placing EPC1 upstream of MYC protein levels. Targeted shRNA knockdown screen, colony-forming assays, transplantation leukemia stem cell assay, transcriptional profiling, pharmacological MYC inhibition, epistasis by concomitant KD Leukemia Medium 24166297
2012 In yeast Piccolo NuA4 complex, the EPcA homology domain of Epl1 (ortholog of human EPC1) contains a short basic region at its N-terminus that is necessary for nucleosomal histone H4/H2A acetyltransferase activity; this basic region is positioned in proximity to the N-terminal histone H2A tail, the globular region of histone H4, and nucleosomal DNA when Piccolo NuA4 is bound to the nucleosome, but is not required for nucleosome binding per se. In vitro nucleosomal histone acetyltransferase assay, site-directed mutagenesis, site-specific cross-linking proximity assay Molecular and cellular biology High 23109429
2017 In S. cerevisiae, deletion of Epl1 (Enhancer of polycomb, ortholog of human EPC1) can be bypassed by loss of the Rpd3L deacetylase complex, a suppression property shared with the catalytic subunit Esa1; dissection of Epl1 domains shows distinct regions are required in vivo for interaction with specific NuA4 subunits, histone acetylation, and chromatin targeting, demonstrating that Epl1 promotes Esa1 catalytic activity through structural scaffolding. Genetic suppressor bypass screen, deletion mapping, in vivo histone acetylation assays, chromatin targeting assays Genetics Medium 28108589
2020 Crystal structure of the MBTD1–EPC1 complex revealed that a hydrophobic C-terminal fragment of EPC1 engages the MBT repeats of MBTD1 at a site distinct from the H4K20me-binding pocket; cellular assays validated key interface residues, establishing that EPC1 recruits MBTD1 into the NuA4/TIP60 complex to influence transcription and DNA repair pathway choice. X-ray crystallography, site-directed mutagenesis, cellular interaction assays (co-IP, functional readouts for DNA repair) Cell reports High 32209463
2024 EPC1 and EPC2 regulate hematopoietic stem and progenitor cell (HSPC) proliferation; depletion of EPC1/2 reduces HSPC numbers in the aorta-gonad mesonephros and caudal hematopoietic tissue by impairing proliferation; mechanistically, EPC1/2 regulate histone H3 acetylation and control expression of DLST (dihydrolipoamide S-succinyltransferase) via H3 acetylation, cooperating with transcription factors SRF and FOXR2. Morpholino/genetic knockdown in zebrafish, K562 cell knockdown, ChIP-based H3 acetylation assays, gene expression analysis iScience Medium 38439957
2026 CCER1 nuclear condensates recruit TIP60 and EPC1 subunits to the NuA4 acetyltransferase complex in spermatids; disruption of CCER1 droplets impairs TIP60–EPC1 interaction and reduces histone H4 hyperacetylation in nucleosomes, leading to defective DNA strand breakage and insufficient histone-to-protamine replacement during spermiogenesis. Immunoprecipitation-mass spectrometry (CCER1-Tag knock-in mice), co-IP validation, H4 acetylation assay, genetic knock-in/knockout in mice Development (Cambridge, England) Medium 41670399

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Consistent rearrangement of chromosomal band 6p21 with generation of fusion genes JAZF1/PHF1 and EPC1/PHF1 in endometrial stromal sarcoma. Cancer research 183 16397222
2013 Novel ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions in ossifying fibromyxoid tumors--molecular characterization shows genetic overlap with endometrial stromal sarcoma. Genes, chromosomes & cancer 141 24285434
1993 Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into the G0 state. The Journal of biological chemistry 104 8473338
2006 Epl1, the major secreted protein of Hypocrea atroviridis on glucose, is a member of a strongly conserved protein family comprising plant defense response elicitors. The FEBS journal 98 16939625
2004 A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner. The Journal of biological chemistry 93 15536069
2015 The Epl1 and Sm1 proteins from Trichoderma atroviride and Trichoderma virens differentially modulate systemic disease resistance against different life style pathogens in Solanum lycopersicum. Frontiers in plant science 62 25755658
2022 Hypoxic pretreatment of adipose-derived stem cell exosomes improved cognition by delivery of circ-Epc1 and shifting microglial M1/M2 polarization in an Alzheimer's disease mice model. Aging 58 35366241
2020 Serum exosomal long noncoding RNAs lnc-FAM72D-3 and lnc-EPC1-4 as diagnostic biomarkers for hepatocellular carcinoma. Aging 52 32554864
2018 Novel EPC1 gene fusions in endometrial stromal sarcoma. Genes, chromosomes & cancer 52 30144186
2015 The Cerato-Platanin protein Epl-1 from Trichoderma harzianum is involved in mycoparasitism, plant resistance induction and self cell wall protection. Scientific reports 52 26647876
2012 Self-assembly at air/water interfaces and carbohydrate binding properties of the small secreted protein EPL1 from the fungus Trichoderma atroviride. The Journal of biological chemistry 51 23250741
2015 Epigenetic factor EPC1 is a master regulator of DNA damage response by interacting with E2F1 to silence death and activate metastasis-related gene signatures. Nucleic acids research 36 26350215
2013 Enhancers of Polycomb EPC1 and EPC2 sustain the oncogenic potential of MLL leukemia stem cells. Leukemia 33 24166297
2017 Involvement of Trichoderma harzianum Epl-1 Protein in the Regulation of Botrytis Virulence- and Tomato Defense-Related Genes. Frontiers in plant science 27 28611802
1995 Analysis of EPC-1 growth state-dependent expression, specificity, and conservation of related sequences. Journal of cellular physiology 27 7814443
2012 Piccolo NuA4-catalyzed acetylation of nucleosomal histones: critical roles of an Esa1 Tudor/chromo barrel loop and an Epl1 enhancer of polycomb A (EPcA) basic region. Molecular and cellular biology 25 23109429
2017 Comparative secretome analysis of Colletotrichum falcatum identifies a cerato-platanin protein (EPL1) as a potential pathogen-associated molecular pattern (PAMP) inducing systemic resistance in sugarcane. Journal of proteomics 21 28546091
2004 The epiplasm gene EPC1 influences cell shape and cortical pattern in Tetrahymena thermophila. The Journal of eukaryotic microbiology 21 15134256
2020 Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex. Cell reports 20 32209463
2017 Chromatin Regulation by the NuA4 Acetyltransferase Complex Is Mediated by Essential Interactions Between Enhancer of Polycomb (Epl1) and Esa1. Genetics 19 28108589
1999 Effects of donor age on the expression of a marker of replicative senescence (EPC-1) in human dermal fibroblasts. Journal of cellular physiology 18 10082127
1993 Expression of an Endopeptidase (EP-C1) in Phaseolus vulgaris Plants. Plant physiology 17 12231697
2018 Functional analysis of eliciting plant response protein Epl1-Tas from Trichoderma asperellum ACCC30536. Scientific reports 16 29789617
2015 The fungal cerato-platanin protein EPL1 forms highly ordered layers at hydrophobic/hydrophilic interfaces. Soft matter 14 25599344
2007 The ectopically parting cells 1-2 (epc1-2) mutant exhibits an exaggerated response to abscisic acid. Journal of experimental botany 13 17426055
1996 The genes encoding the eph-related receptor tyrosine kinase ligands LERK-1 (EPLG1, Epl1), LERK-3 (EPLG3, Epl3), and LERK-4 (EPLG4, Epl4) are clustered on human chromosome 1 and mouse chromosome 3. Genomics 13 8660976
2016 A Study of Cross-Reactivity Between Recombinant EPC1 Antigen of Echinococcus granulosus in Serum from Patients with Confirmed Cystic Echinococcosis Infection and Other Parasitic Infections. The American journal of tropical medicine and hygiene 12 27091868
2018 Evaluation of Echinococcus granulosus recombinant EgAgB8/1, EgAgB8/2 and EPC1 antigens in the diagnosis of cystic echinococcosis in buffaloes. Veterinary parasitology 10 29559147
2022 Evaluation of a novel Echinococcus granulosus recombinant fusion B-EpC1 antigen for the diagnosis of human cystic echinococcosis using indirect ELISA in comparison with a commercial diagnostic ELISA kit. Experimental parasitology 9 35863520
2020 Preliminary Evaluation of Recombinant EPC1 and TPx for Serological Diagnosis of Animal Cystic Echinococcosis. Frontiers in cellular and infection microbiology 9 32426296
2007 Identification of a diagnostic antibody-binding region on the immunogenic protein EpC1 from Echinococcus granulosus and its application in population screening for cystic echinococcosis. Clinical and experimental immunology 9 17403055
2018 Design and construction of a new recombinant fusion protein (2b2t+EPC1) and its assessment for serodiagnosis of cystic echinococcosis. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 8 29696723
2013 Immunoproteomics approach for EPC1 antigenic epitope prediction of G1 and G6 strains of Echinococcus granulosus. Parasitology research 8 23783398
2024 EPC1/2 regulate hematopoietic stem and progenitor cell proliferation by modulating H3 acetylation and DLST. iScience 7 38439957
2019 Design and Construction of a Fusion Peptide Containing B1, B2, B4, and EPC1 Epitopes for Diagnosis of Human Cystic Echinococcosis. Iranian journal of public health 6 31700823
2015 Evaluation of Dot Immunogold Filtration Assay (DIGFA) By Recombinant Protein EPC1 for Anti- Echinococcus granulosus IgG Antibody. Iranian journal of parasitology 5 25904943
2021 Expression and Biological Functions of EPC1 in Nasopharyngeal Carcinoma. Archives of Iranian medicine 2 34841830
2011 [Cloning, expression and immunodiagnostic evaluation of antigen EPC1 from Echinococcus granulosus]. Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 1 21970102
2026 CCER1 condensates participate in histone-to-protamine transition by recruiting the TIP60/EPC1/NuA4 acetyltransferase complex. Development (Cambridge, England) 0 41670399

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