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Symbol EP300 contributors: mct/npt/pgu - updated : 24-01-2016
HGNC name E1A binding protein p300
HGNC id 3373
Corresponding disease
RSTS2 Rubinstein-Taybi syndrome 2
Location 22q13.2      Physical location : 41.488.613 - 41.576.080
Synonym name
  • histone acetyltransferase p300
  • E1A-binding protein, 300kD
  • p300 HAT
  • Synonym symbol(s) CREBBPM, E1ABP, P300, CBP/P300, KAT3B, RSTS2
    TYPE functioning gene
    STRUCTURE 87.47 kb     31 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    31 - 8761 - 2414 - 2009 19539243
    Type widely
    constitutive of
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
    Endocrineparathyroid   highly
     thyroid   highly
    Lymphoid/Immunelymph node   highly
    Nervousnervecranial nerve  moderately
    Reproductivefemale systembreastmammary gland moderately
    Respiratoryrespiratory tractlarynx  predominantly
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text embryonic tissue, placenta
  • a N terminal nuclear receptor interaction motif (LXXLL)
  • three cysteine-histidine rich (C4-H-C3), TAZ, PHD type zinc finger motifs with a CREB (cAMP response element binding protein)
  • a bromodomain between C/H1 and C/H2
  • a KIX domain interacting with FOXO3
  • ZZ zinc finger motif
    interspecies homolog to rattus Ep300 (94.30 pc)
    homolog to murine Ep300 (94.26 pc)
    intraspecies homolog to CREBBP
    CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • chromatin assembly and transcription activation
  • target of adenoviral E1A oncoprotein,structurally and putatively preventing the G0/G1 transition in cell cycle
  • acting as an histone acetyltransferase for the four core histones in nucleosome
  • acetylating and activating TP53 after DNA damage and participating in chromatin remodeling
  • stimulating hypoxia-induced genes such as VEGF
  • involved in DNA repair synthesis
  • regulating acetylation of FEN1
  • coregulating with NCOA1 of the STAT3 transcriptional activity
  • modulating the BRCA1 inhibition of estrogen receptor activity
  • complex CBP/p300 function as co-activators of SOX9 for cartilage tissue-specific gene expression and chondrocyte differentiation
  • playing a crucial role in mediating the functional synergism between PAX8 and TTF-1 in thyroid-specific gene expression
  • activating Sox9-dependent transcription during chondrogenesis
  • can inactivate SIRT2 by acetylation and may regulate the activity of TP53 indirectly through SIRT2 in addition to its direct modification of TP53
  • overexpression of EP300 upregulated PTTG1 at the levels of promoter activity, mRNA and protein expression
  • CREBBP and EP300 function as transcriptional coactivators for a large number of DNA-binding transcription factors involved in multiple signalling and developmental pathways, by modifying lysine residues on both histone and non-histone nuclear proteins
  • may regulate the activity of Sp1 indirectly through HDAC6 in addition to its direct modification of Sp1
  • playing an important role in maintaining genomic integrity by negatively regulating c-myc
  • can regulate NBN-mediated DNA damage response, and these events occur in an acetylation-dependent manner
  • implicated in the acetylation of SPHK1 at a conserved acetylation motif (the GK motif)
  • involved in acetylation of SKP2, which is a process that can be antagonized by the SIRT3 deacetylase
  • KMT2C/KMT2D and H3K27 acetyltransferases CREBBP/EP300 are major enhancer epigenomic writers
  • CELLULAR PROCESS cell cycle
    nucleotide, repair
    nucleotide, transcription, regulation
    CDKN1A-EP300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division
    a component
  • component with CREBBP of a coactivator complex connecting the basal transcriptional machinery to various DNA binding factors
  • component of a ternary complex with TP53 and MDM2
  • binding a complex between MADH1 and STAT3,involved in the cooperative signaling of LIF and BMP2
  • component with CREBBP and IRF3 of the double strand RNA-activated factor DRAF1
  • central role for the ATF5/EP300 complex in ATF5 function, suggesting that coordinated actions by ATF5, EP300, ELK1, and ERK/mitogen-activated protein kinase (MAPK) are essential for ATF5-dependent EGR1 activation and cell proliferation and survival
  • SIK2-EP300-PPARA cascade mediates glucagon effect on ketogenesis
  • binding to the promoter of FTH1 (contributing to its tissue specific expression)
  • binding to scaffold/matrix attachment region (S/MAR) element
  • RNA
    small molecule
  • PAX8 (coactivator of PAX8)
  • binding to HIF1A (coactivation of)
  • binding to PCNA
  • interacting with SIRT2 (triggers the acetylation and subsequent down-regulation of the deacetylation activity of SIRT2, andacetylation of SIRT2 by EP300 relieves the inhibitory effect of SIRT2 on the transcriptional activity of TP53)
  • binding to S/MAR binding protein scaffold attachment factor A (SAF-A)
  • binding to STAT3 and SMAD1
  • SNIP1
  • by its histone acetyltransferase activity, involved in regulation of WT1 transcription
  • transcriptional coactivator p300 may regulate fibronectin expression via PARP and NF-kappaB activation in diabetes
  • interacting PML
  • interacting with EP300 and HDAC1 (acetylation of NR4A1 is modulated by EP300 and HDAC1, suggesting that acetylation is an important post-translational modification for the rapid turnover of NR4A1 protein)
  • MAGEA11 links N-terminal domains of AR and EP300 to promote transcriptional synergy through a cadre of FXXLF-related interacting motifs
  • interacts with the C terminus of PAX5 and acetylates multiple lysine residues within the paired box DNA binding domain of PAX5
  • KLF1 through EKLFTAD2 binds the N-terminal PH domain of the GTF2H1 and four domains of EP300
  • interacting with HDAC9 (induction of adipogenic differentiation promotes HDAC9 down-regulation and replacement by EP300 at the E-box site of the CEBPA gene promoter, thus switching on adipogenic gene expression)
  • PCK1 is acetylated by the EP300 acetyltransferase, and this acetylation stimulates the interaction between PCK1 and UBR5, a HECT domain containing E3 ubiquitin ligase, therefore promoting PCK1 ubiquitinylation and degradation
  • EP300 and SIRT1 were recruited to histone gene promoters in an NPAT-dependent manner
  • ATF3 decreases the interaction of EP300 with PDX1
  • interactions between FOXO3 and the EP300 KIX domain
  • TCF3 and EP300 act in synergy to promote chromatin accessibility of the immunoglobulin &
  • 954; locus
  • chromatin regulators EP300, KDM5A, KDM6A and KDM6B cooperate with KLF4 in promoting the transcription of POU5F1
  • SETD1A, SETD1B and EP300 act cooperatively, through direct interactions and coupled histone modifications, to facilitate the function of TP53
  • CREBBP and EP300 play distinct roles in RA-mediated STRA8 gene transcription
  • KDM1A cooperates with EP300 to facilitate ESR1 protein acetylation and target gene activation upon estrogen stimulation
  • EP300 and KAT2B are two TRIM50 acetyltransferases and the balance between ubiquitination and acetylation regulates TRIM50 degradation
  • KIX domains of CREBBP, and especially EP300, are principal mediators of MYB-dependent gene activation and repression that is required for definitive hematopoiesis
  • binds to and acetylates MTA2 to promote colorectal cancer cells growth
  • EP300 negatively regulates ATAT1 expression and is sequestered on microtubules upon stress
  • CREBBP and EP300 cooperate with several key Treg transcription factors that act on the FOXP3 promoter to promote FOXP3 production
  • EP300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORC at its K81 residue
  • coactivator EP300 mediates cytokine-induced NOS2 transactivation by forming a distant DNA loop between its enhancer and core promoter region
  • EP300 interacts with PPARA through a conserved LXXLL motif and enhances its transcriptional activity
  • CREBBP and EP300, activate transcription of TP53-regulated stress response genes and stabilize TP53 against ubiquitin-mediated degradation
  • when TDG concentrations approach those of histones, TDG acts as a competitive inhibitor of EP300 histone acetylation
  • through its acidic transactivation domain (TAD), RELA has the capacity to form interactions with several different transcriptional regulatory proteins, including GTF2B, GTF2H1, EP300 and TAF9B
  • TGFB1I1 and HIPK1 assist MYB in recruiting the coactivator and acetyltransferase EP300 to chromatin
  • cell & other
    inhibited by the adenovirus oncoprotein E1A
    NAP1L1, binding to the KIX domain
    corresponding disease(s) RSTS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    translocation t (11;22)(q23;q13) in acute myeloid leukemia
    tumoral fusion      
    in acute monocytic leukemia with t(8;22) (p11;q13) (fusion with MYST3)
    tumoral somatic mutation      
    in epithelial cancer
    tumoral fusion      
    fusion genes MYST3-EP300, in acute myeloid leukemia (AML) by chromosomal translocation
    tumoral somatic mutation     loss of function
    in B-cell non-Hodgkin lymphoma
    tumoral fusion      
    EP300-ZNF384 fusion transcript, which is a recurrent alteration in B cell acute lymphoblastic leukemia
    Variant & Polymorphism
    Candidate gene
    Therapy target
    use of histone deacetylase inhibitors has a potential therapy in B-cell non-Hodgkin lymphoma
    inhibition of EP300 abrogates the acetylation of RUNX1-RUNX1T1 and impairs its ability to promote leukemic transformation, and represent a potential therapeutic target in AML