Affinage

EP400

E1A-binding protein p400 · UniProt Q96L91

Length
3159 aa
Mass
343.5 kDa
Annotated
2026-06-09
60 papers in source corpus 30 papers cited in narrative 31 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

EP400 (p400) is the SWI2/SNF2-related ATPase subunit of a large NuA4/TIP60 chromatin-remodeling complex that catalyzes ATP-dependent exchange of canonical histones for the variants H2A.Z and H3.3 at gene promoters and enhancers to control transcription (PMID:11509179, PMID:26669263). EP400 efficiently swaps H2A and H3.1 for H2A.Z and H3.3 in a chromatin- and ATP-stimulated reaction, binds preferentially to acetylated H2A.Z/H3.3 templates, and its remodeling activity is functionally coupled to the TIP60 acetyltransferase, which pre-acetylates H2A.Z before incorporation (PMID:26669263). Deposition of these variants directs context-specific gene programs: EP400 integrates Nanog and H3K4me3 signals at promoters to maintain embryonic stem cell identity (PMID:18614019, PMID:24302573), partners with Sox10 to induce Myrf during oligodendrocyte differentiation (PMID:31081019), controls H2A.Z distribution to silence early regulators (Tfap2a, Pax3) during Schwann cell maturation (PMID:31142747), cooperates with PPARgamma during adipogenesis (PMID:23064015), and forms a complex with NFYA to drive H3.3 deposition and transcription elongation at zygotic genome activation genes, with maternal depletion arresting embryos at the 2-to-4-cell stage (PMID:38493496). Through H2A.Z deposition at the p21 promoter, EP400 represses the p53→p21 axis to permit cell-cycle progression and prevent premature senescence; its loss triggers p53/p21-dependent senescence and is required for the senescence response downstream of VHL (PMID:15655109, PMID:23146670, PMID:18297059). EP400 ATPase activity also destabilizes nucleosomes around DNA double-strand breaks, a step required for RNF8-dependent ubiquitination and recruitment of BRCA1, 53BP1, and Rad51, thereby promoting homologous recombination and NHEJ while restraining mutagenic alternative end-joining (PMID:20876283, PMID:23266955, PMID:26578561). EP400 functions in parallel to SWI/SNF in establishing promoter chromatin accessibility, producing synthetic lethality in cancer cells (PMID:37922899), and is exploited by viral oncoproteins—adenovirus E1A targets EP400 to upregulate Myc and drive transformation, and Merkel cell polyomavirus small T recruits MYCL to the EP400 complex to maintain carcinoma viability (PMID:11509179, PMID:18413597, PMID:29028833).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2001 High

    Established EP400 as the ATPase core of a defined multi-subunit chromatin remodeling complex and linked that complex to viral oncogenic transformation, framing the biochemical identity of the protein.

    Evidence Co-IP and mass spectrometry of the complex plus E1A deletion-mutant transformation assays

    PMID:11509179

    Open questions at the time
    • Catalytic substrate of the ATPase not yet defined
    • Histone variant exchange activity not yet demonstrated
  2. 2005 High

    Placed EP400 as a repressor of the p53→p21 senescence pathway, explaining why loss of this remodeler drives premature senescence.

    Evidence shRNA depletion in human fibroblasts with p53/p21 co-depletion rescue and ChIP at the p21 promoter

    PMID:15655109

    Open questions at the time
    • Molecular mechanism of repression at p21 not yet defined (variant deposition shown later)
    • Whether repression is direct ATPase-dependent unresolved here
  3. 2006 Medium

    Showed EP400 and TIP60 within the same complex have antagonistic, DNA-damage-gated outputs, establishing a switch between proliferative repression and proapoptotic activation.

    Evidence Separate siRNA knockdown of p400 and Tip60 with p21, cell-cycle, and apoptosis readouts

    PMID:16601686

    Open questions at the time
    • Biochemical basis of p400 inhibition of Tip60 not defined
    • Single lab
  4. 2008 High

    Connected EP400 to ESC identity by showing its promoter recruitment depends on H3K4me3 and Nanog, defining how the complex is targeted in pluripotent cells.

    Evidence RNAi screen, p400 ChIP at promoters, Nanog knockdown epistasis in ESCs

    PMID:18614019

    Open questions at the time
    • Direct reader of H3K4me3 within the complex not identified
    • Functional consequence at individual target genes limited
  5. 2008 Medium

    Extended EP400's senescence role downstream of a distinct tumor-suppressor input (VHL) and to oncoprotein-driven apoptosis and Myc activation, broadening its tumor-suppressive and oncogenic context.

    Evidence shRNA epistasis in VHL-inactivated cells; stable RNAi with apoptosis/ARF readouts; co-IP and ChIP at Myc targets

    PMID:15741165 PMID:18297059 PMID:18413597

    Open questions at the time
    • How one remodeler produces both pro- and anti-proliferative outputs not mechanistically unified
    • Single-lab contexts
  6. 2010 High

    Defined EP400's role in DNA double-strand break repair, showing its ATPase destabilizes nucleosomes in gamma-H2AX domains to license downstream ubiquitination and repair-factor recruitment.

    Evidence ATPase-dead mutant analysis, chromatin fractionation, BRCA1/53BP1 recruitment and ubiquitination assays

    PMID:20876283

    Open questions at the time
    • Mechanism of Mdc1-dependent recruitment not fully mapped
    • Histone variant identity at DSBs not resolved here
  7. 2010 High

    Identified EP400 as the catalyst of H2A.Z deposition and tied this activity to hematopoiesis, cell-cycle gene control, and ROS metabolism in vivo.

    Evidence Conditional knockout mouse, H2A.Z deposition assays, cell-cycle FACS, microarray; ROS and ATM-epistasis assays

    PMID:20548951 PMID:20610385

    Open questions at the time
    • Direct in vitro variant-exchange biochemistry not yet shown
    • Relationship of ROS phenotype to variant deposition unclear
  8. 2012 Medium

    Defined EP400 as a homologous recombination factor and a brake on mutagenic alternative end-joining, refining its role to specific DSB repair pathway choice.

    Evidence p400-Rad51 co-IP, HR and alt-EJ reporter assays, CtIP epistasis, PARP inhibitor sensitivity, chromatin decompaction assays

    PMID:23266955 PMID:26578561

    Open questions at the time
    • How EP400 biases pathway choice mechanistically not fully resolved
    • alt-EJ findings single lab
  9. 2012 Medium

    Mechanistically linked EP400-driven H2A.Z deposition at the p21 promoter to senescence onset and to lineage-specific gene activation in adipogenesis, generalizing variant deposition as the effector mechanism.

    Evidence ChIP for H2A.Z/p400 at p21 in young vs senescent cells; Brd8/H2A.Z knockdown and ChIP at PPARgamma targets in 3T3-L1

    PMID:23064015 PMID:23146670

    Open questions at the time
    • Causality between H2A.Z loss and senescence vs correlation not fully disentangled
    • Single-method ChIP studies
  10. 2013 High

    Revealed Hdac6 as an unexpected nuclear partner required for Tip60-p400 target binding in ESCs, expanding the complex's composition in pluripotent cells.

    Evidence Co-purification, ChIP co-localization, fractionation, and differentiation assays in ESCs

    PMID:24302573

    Open questions at the time
    • Catalytic role of Hdac6 in this context excluded but its mechanistic contribution unclear
    • How Hdac6 promotes complex recruitment unknown
  11. 2015 High

    Provided the definitive biochemical demonstration that EP400 exchanges both H2A.Z and H3.3 into chromatin in an ATP-stimulated manner and that double-variant chromatin stimulates transcription.

    Evidence In vitro reconstitution with recombinant histones, in vitro transcription, immobilized chromatin pulldown, and ChIP-seq

    PMID:26669263

    Open questions at the time
    • In vivo coupling of H3.3 and H2A.Z deposition not fully mapped
    • Targeting specificity across the genome incomplete
  12. 2016 Medium

    Mapped a direct, damage-independent ATM-EP400 interaction via the EP400 N-terminus, identifying a constitutive signaling contact relevant to repair.

    Evidence Co-IP, heterologous reconstitution in Sf9 cells, dominant-negative fragment overexpression

    PMID:27814680

    Open questions at the time
    • Functional consequence of the constitutive interaction unclear
    • Single lab
  13. 2017 High

    Demonstrated that Merkel cell polyomavirus small T recruits MYCL to the EP400 complex to activate genes and maintain carcinoma viability, defining a virus-host oncogenic mechanism.

    Evidence Large-scale IP-MS, ChIP-seq, RNA-seq, genome-wide CRISPR screen, transformation assays

    PMID:29028833

    Open questions at the time
    • Which EP400-deposited variants drive target activation not resolved
    • Generalizability beyond MCC unclear
  14. 2019 High

    Established EP400 as a master regulator of myelinating glial differentiation, acting through Sox10/Myrf in oligodendrocytes and via H2A.Z redistribution that silences early regulators in Schwann cells.

    Evidence Conditional and temporally controlled knockout mice, ChIP/ChIP-seq, Ep400-Sox10 co-IP, Tfap2a double-knockout rescue

    PMID:31081019 PMID:31142747

    Open questions at the time
    • How EP400 chooses which loci to clear H2A.Z from not defined
    • Maintenance vs differentiation roles delineated but molecular switch unknown
  15. 2021 Medium

    Resolved sub-complex heterogeneity by identifying JAZF1/MBTD1-containing and Phf5a-stabilized assemblies that couple TIP60 acetylation and variant deposition at specific loci and during class switch recombination.

    Evidence MS complex characterization, H2A.Z acetylation ChIP-seq after JAZF1 depletion; siRNA screen, ChIP, and DSB repair reporters at switch regions

    PMID:33445503 PMID:33938017

    Open questions at the time
    • Functional division of labor among sub-complexes incomplete
    • Recruitment determinants of each sub-complex unclear
  16. 2023 High

    Positioned EP400 in a chromatin-accessibility pathway parallel to SWI/SNF at promoters, revealing synthetic lethality with therapeutic relevance, and tied the complex to neural crest metabolism and morphogenesis.

    Evidence Fast-acting SWI/SNF inhibitor with ATAC-seq and EP400-depletion epistasis; conditional KO with metabolic and proliferation analyses

    PMID:37024457 PMID:37922899

    Open questions at the time
    • Why EP400 compensates at promoters but not enhancers unexplained
    • Metabolic phenotype mechanism in neural crest not resolved
  17. 2024 High

    Defined EP400's earliest developmental role: NFYA-directed H3.3 deposition at zygotic genome activation genes driving transcription elongation, with maternal loss causing 2-to-4-cell arrest.

    Evidence Oocyte-specific conditional KO, EP400-NFYA co-IP, H3.3 ChIP-seq, RNA-seq, embryo assays

    PMID:38493496

    Open questions at the time
    • How NFYA targeting is coordinated with H2A.Z deposition unclear
    • Link to mitochondrial gene activation mechanistically thin
  18. 2025 High

    Revealed EP400 as a restrictor of HIV-1 transcription through paused-RNAPII control, with DMAP1 directly blocking Tat-TAR engagement, defining a Tat-dependent latency mechanism.

    Evidence shRNA screens, EP400/DMAP1/RNAPII ChIP-seq, DMAP1-Tat co-IP, Tat-deficient virus and RNAPII Ser2 phosphorylation assays, primary CD4+ T cells

    PMID:40842241 PMID:41414674

    Open questions at the time
    • Whether ATPase/variant-deposition activity is required for latency unresolved
    • Generalization to cellular paused genes incomplete
  19. 2025 Medium

    Clarified the catalytic coupling within the complex, showing TIP60 pre-acetylates H2A.Z to promote its loading by EP400, and identified upstream PRMT5/SRSF1 control of complex integrity via KAT5 splicing.

    Evidence EP400 rapid-depletion ChIP-seq/ATAC-seq and biochemistry (preprint); Iso-Seq/RNA-seq with PRMT5 inhibition in MCC cells

    PMID:40846633

    Open questions at the time
    • Acetylation-coupling model awaits peer review
    • Direct structural basis of H2A.Zac-H2B handoff not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EP400 achieves locus-specific targeting and reconciles its dual roles as a transcriptional activator and repressor across diverse cellular contexts remains unresolved.
  • No unified model linking sub-complex composition to activating vs repressive outcomes
  • Recruitment code beyond H3K4me3/Nanog/Sox10/NFYA incomplete
  • Structural basis of variant exchange and acetylation coupling unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-73894 DNA Repair 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
DMAP1JAZF1KAT5MYCNFYARAD51SOX10TRRAP
Complex memberships
NuA4/TIP60 complexp400/Domino complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 EP400 (p400) is a SWI2/SNF2-related 400 kDa ATPase that forms a large chromatin-remodeling complex with TRRAP/PAF400, DNA helicases TAP54alpha/beta, actin-like proteins, and the human Enhancer of Polycomb homolog. E1A binds this complex, and an E1A mutant defective in p400 binding is also defective in transformation, establishing p400 complex formation as essential for E1A-mediated transformation. Co-immunoprecipitation, mass spectrometry identification of complex components, E1A deletion mutant analysis, partial rescue with p400 fragments Cell High 11509179
2005 p400 is a component of the p53→p21 senescence pathway: acute shRNA depletion of p400 causes premature senescence in human fibroblasts (G1 arrest, p21 induction, SAHF, beta-gal staining), and these phenotypes are rescued by co-expression of p53-shRNA or p21-shRNA. p400 complex co-localizes with p53 on the p21 promoter, indicating p400 inhibits p53→p21 transcription. shRNA knockdown, co-immunoprecipitation/ChIP showing p400 at p21 promoter, genetic epistasis via co-depletion of p53/p21 Genes & development High 15655109
2005 p400 is required for E1A-induced apoptosis: E1A increases p400 expression and promotes co-association of p400-TRRAP with Rb; suppression of p400 by stable RNAi reduces ARF, p53 levels, and apoptosis in E1A-expressing cells. p400 is identified as a regulator of the ARF-p53 pathway. Stable RNAi knockdown, measurement of ARF/p53/apoptosis levels, co-immunoprecipitation of p400-TRRAP-Rb The Journal of biological chemistry Medium 15741165
2006 Tip60 and p400 (within the same complex) play antagonistic roles: p400 represses p21 expression in unstressed cells (allowing cell cycle progression), while Tip60 activates p53 target proapoptotic genes. p400 inhibits Tip60 function in the absence of DNA damage, and this inhibition is abolished after DNA damage. Both are required for UV-induced apoptosis. siRNA knockdown of p400 and Tip60 separately, measurement of p21 expression, cell cycle analysis, apoptosis assays, functional epistasis The EMBO journal Medium 16601686
2008 VHL loss-induced senescence requires p400 (and Rb): acute VHL inactivation causes a senescent-like phenotype that is independent of p53 and HIF but dependent on Rb and the SWI2/SNF2 chromatin remodeler p400, placing p400 downstream of VHL in a tumor-suppressive senescence pathway. Genetic epistasis using shRNA against p400 and Rb in VHL-inactivated cells, in vitro and in vivo senescence assays Nature cell biology Medium 18297059
2008 In embryonic stem cells, p400 localization to promoters of both silent and active genes depends on H3K4me3, and Nanog depletion reduces p400 binding to target promoters without affecting H3K4me3 levels, indicating Tip60-p400 integrates Nanog and H3K4me3 signals to regulate ESC gene expression. RNAi screen, ChIP for p400 at promoters, Nanog knockdown epistasis, gene expression profiling Cell High 18614019
2008 E1A targets p400 to stabilize and upregulate the oncoprotein Myc: E1A promotes coassociation of Myc and p400 at Myc target genes, leading to transcriptional induction. Forced Myc expression rescues activity of an E1A mutant defective in p400 binding, establishing Myc as the downstream target of the E1A-p400 interaction. Co-immunoprecipitation, ChIP at Myc target genes, RNAi, rescue with Myc overexpression, E1A p400-binding mutant analysis Proceedings of the National Academy of Sciences of the United States of America Medium 18413597
2010 p400 ATPase activity and Tip60 acetyltransferase cooperate during DNA double-strand break (DSB) repair: p400 is recruited to DSBs by a mechanism independent of ATM but requiring Mdc1. p400 ATPase activity destabilizes nucleosomes in gamma-H2AX domains surrounding DSBs, which is required for RNF8-dependent chromatin ubiquitination and subsequent recruitment of BRCA1 and 53BP1. Chromatin fractionation, ATPase-dead mutant analysis, siRNA knockdown, recruitment assays for BRCA1/53BP1, ubiquitination assays The Journal of cell biology High 20876283
2010 p400 is required for correct control of ROS metabolism: p400 depletion increases intracellular ROS levels and causes DNA damage. The effects of p400 on cell cycle progression, apoptosis, and senescence are dependent on ATM-dependent DDR pathways and involve direct transcriptional regulation of specific promoters including those controlling ROS metabolism. siRNA knockdown, ROS measurement, ATM siRNA epistasis, ChIP at specific promoters PLoS genetics Medium 20548951
2010 p400/mDomino catalyzes ATP-dependent deposition of histone variant H2A.Z into nucleosomes to regulate gene expression, and is essential for adult bone marrow hematopoiesis and cell-cycle progression. Loss of p400/mDomino in MEFs causes S and G2/M phase defects, polyploidy, and multinucleation, with impaired expression of FoxM1 and c-Myc target cell-cycle genes. Conditional knockout mouse (Mx1-Cre), hematopoietic colony assay, cell-cycle FACS, DNA microarray, H2A.Z deposition assays The Journal of biological chemistry High 20610385
2012 p400 ATPase is required for DNA repair by homologous recombination (HR): p400-depleted cells are defective in HR-dependent repair, Rad51 recruitment to DSBs, and homology-directed repair. p400 and Rad51 are found in the same complex and both promote chromatin remodeling (decompaction) around DSBs. Co-immunoprecipitation of p400-Rad51 complex, siRNA knockdown, Rad51 focus formation assay, HR reporter assay, chromatin remodeling assay The Journal of cell biology High 23266955
2012 p400 deposits H2A.Z within the p21 promoter to repress p21 gene expression. During replicative senescence of IMR-90 fibroblasts, p400 levels decline and H2A.Z is lost from the p21 promoter, contributing to sustained p21 transcription and senescence onset. ChIP for H2A.Z and p400 at p21 promoter, nucleosome mapping, comparison between young and senescent cells Mechanisms of ageing and development Medium 23146670
2012 The p400/Brd8 complex promotes adipogenesis by incorporating histone variant H2A.Z at PPARgamma target gene promoters; shRNA-mediated knockdown of Brd8 or H2A.Z abolishes 3T3-L1 preadipocyte differentiation and blocks accumulation of PPARgamma, p400, and RNA Pol II at PPARgamma target genes. shRNA knockdown, lipid accumulation assay, ChIP for p400/PPARgamma/H2A.Z/Pol II at target gene promoters Endocrinology Medium 23064015
2013 Hdac6 co-purifies with Tip60-p400 complex from embryonic stem cells and is required for Tip60-p400 binding to many of its target genes. Unlike differentiated cells where Hdac6 is cytoplasmic, Hdac6 is largely nuclear in ESCs and interacts with Tip60-p400. Hdac6 does not appear to deacetylate histones in this context but is necessary for robust ESC differentiation. Co-purification/co-IP, ChIP for Hdac6 and Tip60-p400 at target promoters, siRNA knockdown, cellular fractionation, differentiation assays eLife High 24302573
2015 EP400 deposits histone H3.3 into promoters and enhancers during gene activation alongside H2AZ. EP400 binds preferentially to acetylated H2AZ/H3.3-containing chromatin templates and is required for transcription stimulation by double-variant chromatin in vitro. EP400 efficiently exchanges H2A and H3.1 with H2AZ and H3.3, respectively, in a chromatin- and ATP-stimulated manner in vitro. Biochemical reconstitution of chromatin templates, in vitro transcription assay, histone exchange assay with recombinant histones, immobilized chromatin pulldown, ChIP-seq in vivo Molecular cell High 26669263
2015 p400 ATPase acts as a brake on alternative end-joining (alt-EJ) DNA repair: p400 depletion increases alt-EJ frequency, generates large deletions after DSB repair, and this increase is dependent on CtIP-mediated resection. p400 depletion also leads to PARP and DNA ligase 3 recruitment to DSBs, conferring sensitivity to PARP inhibitors. Intracellular reporter substrates for alt-EJ, siRNA knockdown, CtIP epistasis, PARP inhibitor sensitivity assay, immunofluorescence for PARP/ligase 3 recruitment Nucleic acids research Medium 26578561
2016 ATM kinase physically interacts with p400 ATPase independently of DNA damage state via the N-terminal domain of p400. This interaction can be reconstituted in Sf9 insect cells without mammalian bridging proteins, and overexpression of ATM-interacting p400 N-terminal fragments acts as a dominant negative, inhibiting DNA damage repair and cell proliferation. Co-immunoprecipitation, heterologous reconstitution in Sf9 cells, dominant-negative overexpression, DNA repair and proliferation assays BMC molecular biology Medium 27814680
2017 Merkel cell polyomavirus Small T antigen binds MYCL and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. The ST-MYCL-EP400 complex binds together at specific gene promoters and activates their expression. MYCL and EP400 are required for maintenance of MCC cell viability and cooperate with ST to promote gene expression and cellular transformation. Large-scale immunoprecipitation with mass spectrometry, ChIP-seq, RNA-seq, CRISPR-Cas9 genome-wide screen, transformation assays PLoS pathogens High 29028833
2019 Ep400 is required for oligodendrocyte terminal differentiation and myelination: Ep400-deficient oligodendrocyte precursors develop normally but fail to terminally differentiate. Mechanistically, Ep400 interacts with transcription factor Sox10, binds to regulatory regions of the Myrf gene, and is required to induce Myrf, a central transcriptional regulator of myelination. Ep400 deletion in mature oligodendrocytes causes no phenotype, indicating Ep400 is dispensable for myelin maintenance. Conditional knockout mouse, ChIP for Ep400 at Myrf regulatory regions, co-immunoprecipitation of Ep400-Sox10, histological and myelin staining, immunofluorescence Nucleic acids research High 31081019
2019 Ep400 deletion in Schwann cells causes peripheral neuropathy through terminal differentiation defects. Mechanistically, Ep400 absence alters H2A.Z genomic distribution, causing H2A.Z to remain at promoters of early developmental regulators (Tfap2a, Pax3). Deletion of Tfap2a in Ep400-deficient Schwann cells provides partial rescue, indicating persistent expression of early regulators (maintained by Ep400 loss) mediates the defect. Conditional knockout mouse, ChIP-seq for H2A.Z distribution, genetic epistasis (double knockout with Tfap2a), histological analysis of peripheral nerves Nature communications High 31142747
2021 JAZF1 is a member of a p400 sub-complex containing MBTD1 (but excluding ANP32E), identified by mass spectrometry-based H2A variant chaperone complex characterization. JAZF1 depletion leads to reduced H2A.Z acetylation at >1000 regulatory sites without affecting H2A.Z nucleosome positioning, suggesting JAZF1 recruits TIP60 acetyltransferase activity to regulate H2A.Z acetylation. Mass spectrometry identification of complex composition, ChIP-seq for H2A.Z acetylation after JAZF1 depletion, RNA-seq International journal of molecular sciences Medium 33445503
2021 Phf5a stabilizes the p400 histone chaperone complex at immunoglobulin switch regions, which promotes deposition of H2A variants (H2AX and H2A.Z) critical for early DNA damage response and NHEJ, respectively, during class switch recombination. Depletion of Phf5a or p400 blocks repair of AID-induced and I-SceI-induced DNA DSBs. siRNA screen, ChIP for p400 at switch regions, H2A variant deposition assays, I-SceI reporter for DSB repair, flow cytometric CSR assay The EMBO journal Medium 33938017
2023 EP400/TIP60 remodeler compensates for loss of SWI/SNF activity by reestablishing chromatin accessibility at most gene promoters (but not enhancers) during prolonged SWI/SNF inhibition. EP400 and SWI/SNF show synthetic lethality in cancer cell lines. This places EP400 in a parallel chromatin accessibility pathway to SWI/SNF at promoters. Fast-acting SWI/SNF inhibitor treatment, ATAC-seq for chromatin accessibility, genetic epistasis with EP400 depletion, synthetic lethality in cancer cell lines Cell High 37922899
2023 Inactivation of Ep400 (or Kat5/Tip60) in cranial neural crest cells severely impairs carbohydrate and amino acid metabolism, decreases protein synthesis, proliferation, and survival of neural crest cells, leading to loss of most facial structures. Heterozygous Kat5 loss impairs palatogenesis, implicating the Tip60/Ep400 complex in facial morphogenesis. CRISPR/Cas9 genome editing and conditional mutagenesis in mouse, metabolic analysis, histology, immunofluorescence for proliferation/survival markers International journal of oral science Medium 37024457
2024 EP400 deposits H3.3 into promoters of major zygotic genome activation (ZGA) genes in mouse oocytes and early embryos. EP400 forms a protein complex with NFYA at ZGA gene promoters, modulates H3.3 distribution between euchromatin and heterochromatin, promotes transcription elongation, and activates genes regulating mitochondrial functions and TCA cycle enzymes. Maternal Ep400 depletion causes developmental arrest at the 2-to-4-cell stage. Oocyte-specific conditional knockout, co-immunoprecipitation of EP400-NFYA, ChIP-seq for H3.3 distribution, RNA-seq, embryo developmental assays Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 38493496
2024 Adenovirus small e1a promotes derepression of Alu retrotransposons via physical interaction with EP400 chromatin remodeler at YAP/TEAD- and AP-1-bound enhancers; EP400 ablation abrogates e1a-induced Alu derepression. This establishes EP400 as required for e1a-mediated epigenomic changes at enhancer Alus. EP400 ChIP-seq, ATAC-seq/epigenome profiling, EP400 ablation by CRISPR, RNA-seq for Alu transcription, co-immunoprecipitation of e1a-EP400 Nucleic acids research Medium 39011896
2024 EP400 suppresses melanoma cell growth via interaction with c-MYC: a LINC00944-encoded peptide disrupts the EP400-MYC interaction, reduces c-MYC protein expression, and represses MYC transcriptional activity including fatty acid and glucose metabolism target genes. Co-immunoprecipitation of EP400-MYC complex, peptide competition assay, MYC reporter/expression assays, cell proliferation assays Biochemical pharmacology Low 39586403
2025 The p400 complex promotes HIV-1 latency by suppressing viral transcription: EP400 and its complex partner DMAP1 co-localize with paused RNA Polymerase II at transcriptional start sites, and their depletion markedly increases RNAPII pause release at the HIV-1 locus. EP400 depletion also increases expression of T-cell factors that activate HIV-1 transcription. shRNAmir pooled screen, ChIP-seq for EP400/DMAP1/RNAPII at HIV locus and cellular genes, HIV transcription reporter assays, primary CD4+ T cell assays Nucleic acids research Medium 40842241
2025 EP400 ATPase (with DMAP1) restricts HIV-1 transcription in a Tat-dependent manner: EP400 associates with RNAPII C-terminal domain, while DMAP1 directly binds the viral transactivator Tat's basic domain, blocking Tat-TAR RNA interaction and limiting p-TEFb-mediated RNAPII Ser2 phosphorylation and elongation. Repression requires simultaneous interactions among EP400, DMAP1, and Tat. Co-immunoprecipitation of DMAP1-Tat, EP400-RNAPII interaction assays, ChIP-seq, Tat-deficient virus experiments, RNAPII Ser2 phosphorylation assays Nucleic acids research High 41414674
2025 PRMT5 sustains the Tip60-EP400 complex in Merkel cell carcinoma via SRSF1: PRMT5-mediated modification of SRSF1 enhances its recruitment to m6A-modified RNA, ensuring proper KAT5 (Tip60) splicing and Tip60-EP400 activity. PRMT5 inhibition disrupts SRSF1 recruitment, leading to splicing defects (exon skipping, intron retention) in KAT5 transcripts and impaired Tip60-EP400 complex activity. RNA-seq, Iso-Seq for alternative splicing analysis, PRMT5 inhibition, SRSF1 modification assays, complex activity assays in MCC cells Life science alliance Medium 40846633
2025 EP400 (within NuA4/TIP60) pre-acetylates H2A.Z to facilitate H2A.Zac-H2B dimer association with the complex before EP400-mediated incorporation into chromatin at gene promoters, positively regulating transcription. This establishes a coordinated mechanism where TIP60 acetyltransferase activity and EP400 remodeling activity are functionally coupled. EP400 rapid depletion system, functional genomics (ChIP-seq, ATAC-seq), biochemical analyses of H2A.Z acetylation and chromatin incorporation bioRxivpreprint Medium

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400. Nature 973 2554142
2008 An RNAi screen of chromatin proteins identifies Tip60-p400 as a regulator of embryonic stem cell identity. Cell 359 18614019
1990 A cerebellar Purkinje cell marker P400 protein is an inositol 1,4,5-trisphosphate (InsP3) receptor protein. Purification and characterization of InsP3 receptor complex. The EMBO journal 267 2153079
2001 The p400 complex is an essential E1A transformation target. Cell 262 11509179
2008 VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nature cell biology 200 18297059
2010 The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair. The Journal of cell biology 156 20876283
1989 Developmental expression and intracellular location of P400 protein characteristic of Purkinje cells in the mouse cerebellum. Developmental biology 138 2707487
1988 Purification and characterization of P400 protein, a glycoprotein characteristic of Purkinje cell, from mouse cerebellum. Journal of neurochemistry 136 3141586
1990 Expressed cerebellar-type inositol 1,4,5-trisphosphate receptor, P400, has calcium release activity in a fibroblast L cell line. Neuron 131 2164403
1991 Immunohistochemical localization of an inositol 1,4,5-trisphosphate receptor, P400, in neural tissue: studies in developing and adult mouse brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 122 1648604
2005 The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway. Genes & development 117 15655109
2017 Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis. PLoS pathogens 107 29028833
2015 EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation. Molecular cell 102 26669263
1979 Biochemical and immunological studies on the P400 protein, a protein characteristic of the Purkinje cell from mouse and rat cerebellum. Developmental neuroscience 84 121073
2009 The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways. Oncogene 83 19169279
2006 Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression. The EMBO journal 80 16601686
2023 Global identification of SWI/SNF targets reveals compensation by EP400. Cell 69 37922899
2012 The chromatin remodeler p400 ATPase facilitates Rad51-mediated repair of DNA double-strand breaks. The Journal of cell biology 61 23266955
1989 Phosphorylation of P400 protein by cyclic AMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase II. Journal of neurochemistry 60 2547906
2013 Hdac6 regulates Tip60-p400 function in stem cells. eLife 54 24302573
2005 p400 is required for E1A to promote apoptosis. The Journal of biological chemistry 44 15741165
1985 P400 protein characteristic to Purkinje cells and related proteins in cerebella from neuropathological mutant mice: autoradiographic study by 14C-leucine and phosphorylation. Developmental neuroscience 37 4076002
2019 Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system. Nucleic acids research 34 31081019
2008 Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc. Proceedings of the National Academy of Sciences of the United States of America 34 18413597
2013 Ossifying fibromyxoid tumor presenting EP400-PHF1 fusion gene. Human pathology 31 23806526
2007 Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic hematopoiesis. Genes to cells : devoted to molecular & cellular mechanisms 31 17535249
2010 Essential role of p400/mDomino chromatin-remodeling ATPase in bone marrow hematopoiesis and cell-cycle progression. The Journal of biological chemistry 30 20610385
2019 Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy. Nature communications 26 31142747
2024 Variants in EP400, encoding a chromatin remodeler, cause epilepsy with neurodevelopmental disorders. American journal of human genetics 25 39708813
2010 The E1A-associated p400 protein modulates cell fate decisions by the regulation of ROS homeostasis. PLoS genetics 25 20548951
1993 Distribution of the inositol 1,4,5-trisphosphate receptor, P400, in adult rat brain. The Journal of comparative neurology 25 8282854
2021 JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.Z Acetylation at Regulatory Regions. International journal of molecular sciences 24 33445503
2012 The p400/Brd8 chromatin remodeling complex promotes adipogenesis by incorporating histone variant H2A.Z at PPARγ target genes. Endocrinology 24 23064015
1990 Architecture of Purkinje cells of the reeler mutant mouse observed by immunohistochemistry for the inositol 1,4,5-trisphosphate receptor protein P400. Neuroscience research 24 1699178
2021 Phf5a regulates DNA repair in class switch recombination via p400 and histone H2A variant deposition. The EMBO journal 20 33938017
2021 Exosomes From M2 Macrophage Promote Peritendinous Fibrosis Posterior Tendon Injury via the MiR-15b-5p/FGF-1/7/9 Pathway by Delivery of circRNA-Ep400. Frontiers in cell and developmental biology 20 34513819
2007 p400 function is required for the adenovirus E1A-mediated suppression of EGFR and tumour cell killing. Oncogene 19 17486071
2015 Control of alternative end joining by the chromatin remodeler p400 ATPase. Nucleic acids research 17 26578561
2020 The Aedes aegypti Domino Ortholog p400 Regulates Antiviral Exogenous Small Interfering RNA Pathway Activity and ago-2 Expression. mSphere 14 32269152
2013 The temozolomide derivative 2T-P400 inhibits glioma growth via administration route of intravenous injection. Journal of neuro-oncology 14 24065569
2024 Chromatin Modifier EP400 Regulates Oocyte Quality and Zygotic Genome Activation in Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 38493496
2020 TIP60/P400/H4K12ac Plays a Role as a Heterochromatin Back-up Skeleton in Breast Cancer. Cancer genomics & proteomics 10 33099470
2012 Decrease of p400 ATPase complex and loss of H2A.Z within the p21 promoter occur in senescent IMR-90 human fibroblasts. Mechanisms of ageing and development 9 23146670
2023 The Tip60/Ep400 chromatin remodeling complex impacts basic cellular functions in cranial neural crest-derived tissue during early orofacial development. International journal of oral science 8 37024457
2019 In silico identification of EP400 and TIA1 as critical transcription factors involved in human hepatocellular carcinoma relapse. Oncology letters 8 31897208
2011 Loss of H2A.Z Is Not Sufficient to Determine Transcriptional Activity of Snf2-Related CBP Activator Protein or p400 Complexes. International journal of cell biology 8 21785598
1994 Subcellular localization of the inositol 1,4,5-trisphosphate receptor, P400, in the vestibular complex and dorsal cochlear nucleus of the rat. Brain research 8 8131069
2016 Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response. BMC molecular biology 7 27814680
1992 P400 protein is one of the major substrates for Ca2+/calmodulin-dependent protein kinase II in the postsynaptic density-enriched fraction isolated from rat cerebral cortex, hippocampus and cerebellum. Neurochemistry international 7 1338970
2022 Analysis of adherent cell culture lysates with low metabolite concentrations using the Biocrates AbsoluteIDQ p400 HR kit. Scientific reports 5 35562573
1991 Immunohistochemical expression of P400 protein in Purkinje cells of sphingomyelinosis mouse. Brain & development 5 1892215
2024 Adenovirus small E1A directs activation of Alu transcription at YAP/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodeler. Nucleic acids research 3 39011896
2025 The p400 complex promotes HIV-1 latency by suppressing viral transcription and altering the host cell state. Nucleic acids research 2 40842241
2021 A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models. Translational psychiatry 2 33602898
2024 A peptide encoded by LINC00944 suppresses the growth of melanoma cells by diminishing EP400-MYC interaction. Biochemical pharmacology 1 39586403
2026 The potent and selective adenosine A2AR antagonists P400 and P625 protect against symptoms in autoimmune experimental encephalomyelitis by attenuating neuroinflammation and demyelination. Neuropharmacology 0 41610910
2026 Integrated Multi-omic Profiling Identifies BRD8/EP400 as a Pivotal Chromatin Module Mediating Anti-HER2 Response in HR+/HER2+ Breast Cancer. Cancer research 0 41886605
2025 Protein arginine methyltransferase 5 sustains Tip60-EP400 complex via SRSF1 in Merkel cell carcinoma. Life science alliance 0 40846633
2025 Ossification-deficient atypical ossifying fibromyxoid tumor of submandibular gland with PHF1::EP400 fusion: diagnostic challenges. Oral and maxillofacial surgery 0 41068353
2025 The human chromatin remodeling complex p400 restricts HIV-1 transcription in a Tat-dependent manner. Nucleic acids research 0 41414674

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