EP300

This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer. [provided by RefSeq, Jul 2008]

E1A Binding Protein P300

Functions as histone acetyltransferase and regulates transcription via chromatin remodeling (PubMed:23415232, PubMed:23934153, PubMed:8945521).

Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation (PubMed:23415232, PubMed:23934153, PubMed:8945521).

Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-27' (H3K27ac) (PubMed:23911289).

Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1 or SIRT2 (PubMed:12929931, PubMed:16762839, PubMed:18722353).

Acetylates 'Lys-131' of ALX1 and acts as its coactivator (PubMed:12929931).

Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function (PubMed:18722353).

Acetylates HDAC1 leading to its inactivation and modulation of transcription (PubMed:16762839).

Acetylates 'Lys-247' of EGR2 (By similarity).

Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2 (PubMed:12586840).

Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity (PubMed:15890677).

Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity (PubMed:12402037).

Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter (PubMed:14645221).

Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity (PubMed:16617102).

Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity (PubMed:20955178).

Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902).

Acetylates MEF2D (PubMed:21030595).

Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degragation, this mechanism may be involved in CD4/CD8 lineage differentiation (PubMed:20810990).

Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (By similarity).

In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA), 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), lactoyl-CoA or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation or propionylation, respectively (PubMed:17267393, PubMed:25818647, PubMed:29775581, PubMed:31645732).

Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25818647).

Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (2E)-butenoyl-CoA (crotonyl-CoA) concentration is low (PubMed:25818647).

Also acts as a histone butyryltransferase; butyrylation marks active promoters (PubMed:17267393).

Catalyzes histone lactylation in macrophages by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription (PubMed:31645732).

Acts as a protein-lysine 2-hydroxyisobutyryltransferase; regulates glycolysis by mediating 2-hydroxyisobutyrylation of glycolytic enzymes (PubMed:29775581).

Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493).

Acetylates PCK1 and promotes PCK1 anaplerotic activity (PubMed:30193097).

Acetylates RXRA and RXRG (PubMed:17761950).

(Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein.

Animal organ morphogenesis Source: Ensembl
Apoptotic process Source: UniProtKB
B cell differentiation Source: Ensembl
Behavioral defense response Source: Ensembl
Cell cycle Source: UniProtKB-KW
Cellular response to UV Source: UniProtKB
Circadian rhythm Source: UniProtKB
Face morphogenesis Source: Ensembl
Fat cell differentiation Source: UniProtKB
Heart development Source: Ensembl
Histone acetylation Source: UniProtKB
Histone H2B acetylation Source: UniProtKB
Histone H3-K56 acetylation Source: Ensembl
Histone H4 acetylation Source: UniProtKB
Internal peptidyl-lysine acetylation Source: UniProtKB
Internal protein amino acid acetylation Source: UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
Learning or memory Source: Ensembl
Lung development Source: Ensembl
Macrophage derived foam cell differentiation Source: UniProtKB
Megakaryocyte development Source: Ensembl
Multicellular organism growth Source: Ensembl
Negative regulation of gluconeogenesis Source: UniProtKB
Negative regulation of protein-containing complex assembly Source: ARUK-UCL
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Nervous system development Source: ARUK-UCL
N-terminal peptidyl-lysine acetylation Source: UniProtKB
Peptidyl-lysine acetylation Source: ARUK-UCL
Peptidyl-lysine butyrylation Source: UniProtKB
Peptidyl-lysine crotonylation Source: UniProtKB
Peptidyl-lysine propionylation Source: UniProtKB
Platelet formation Source: Ensembl
Positive regulation by host of viral transcription Source: BHF-UCL
Positive regulation of DNA-binding transcription factor activity Source: UniProtKB
Positive regulation of gene expression, epigenetic Source: UniProtKB
Positive regulation of neuron projection development Source: ARUK-UCL
Positive regulation of NF-kappaB transcription factor activity Source: ARUK-UCL
Positive regulation of NIK/NF-kappaB signaling Source: ARUK-UCL
Positive regulation of protein binding Source: Ensembl
Positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding Source: ARUK-UCL
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: UniProtKB
Positive regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
Protein acetylation Source: UniProtKB
Protein destabilization Source: UniProtKB
Protein stabilization Source: UniProtKB
Regulation of androgen receptor signaling pathway Source: BHF-UCL
Regulation of autophagy Source: ParkinsonsUK-UCL
Regulation of cellular response to heat Source: Reactome
Regulation of glycolytic process Source: UniProtKB
Regulation of mitochondrion organization Source: UniProtKB
Regulation of signal transduction by p53 class mediator Source: Reactome
Regulation of tubulin deacetylation Source: UniProtKB
Response to estrogen Source: UniProtKB
Response to hypoxia Source: UniProtKB
Skeletal muscle tissue development Source: Ensembl
Somitogenesis Source: Ensembl
Stimulatory C-type lectin receptor signaling pathway Source: Reactome
Swimming Source: Ensembl
Thigmotaxis Source: Ensembl

Nucleus; Cytoplasm; Chromosome. Localizes to active chromatin: Colocalizes with histone H3 acetylated and/or crotonylated at 'Lys-18' (H3K18ac and H3K18cr, respectively) (PubMed:25818647). In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. Colocalizes with ROCK2 in the nucleus (PubMed:12929931).

Defects in EP300 may play a role in epithelial cancer.
Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A.
Rubinstein-Taybi syndrome 2 (RSTS2):
A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients.
Menke-Hennekam syndrome 2 (MKHK2):
A form of Menke-Hennekam syndrome, a congenital autosomal dominant disease characterized by developmental delay, growth retardation, and craniofacial dysmorphism. Patients have intellectual disability of variable severity, speech delay, autistic behavior, short stature and microcephaly. Main facial characteristics include short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum.

Acetylated on Lys at up to 17 positions by intermolecular autocatalysis. Deacetylated in the transcriptional repression domain (CRD1) by SIRT1, preferentially at Lys-1020. Deacetylated by SIRT2, preferentially at Lys-418, Lys-423, Lys-1542, Lys-1546, Lys-1549, Lys-1699, Lys-1704 and Lys-1707.
Citrullinated at Arg-2142 by PADI4, which impairs methylation by CARM1 and promotes interaction with NCOA2/GRIP1.
Methylated at Arg-580 and Arg-604 in the KIX domain by CARM1, which blocks association with CREB, inhibits CREB signaling and activates apoptotic response. Also methylated at Arg-2142 by CARM1, which impairs interaction with NCOA2/GRIP1.
Sumoylated; sumoylation in the transcriptional repression domain (CRD1) mediates transcriptional repression. Desumoylated by SENP3 through the removal of SUMO2 and SUMO3.
Probable target of ubiquitination by FBXO3, leading to rapid proteasome-dependent degradation.
Phosphorylated by HIPK2 in a RUNX1-dependent manner. This phosphorylation that activates EP300 happens when RUNX1 is associated with DNA and CBFB. Phosphorylated by ROCK2 and this enhances its activity. Phosphorylation at Ser-89 by AMPK reduces interaction with nuclear receptors, such as PPARG.