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EP300

GeneName

EP300

Summary

EP300, also known as P300 or p300 HAT, is a 264 kDa histone acetyltransferase that plays a crucial role in the regulation of gene expression. It is predominantly localised in the nucleus, where it functions as a transcription coactivator by acetylating histones and non-histone proteins, thereby influencing chromatin structure and transcriptional activity. EP300 is involved in various biological pathways, including cellular responses to stress, development processes, and immune responses. Its ability to bind to multiple transcription factors, such as NF-kappaB and p53, highlights its importance in regulating diverse cellular processes, including apoptosis, differentiation, and morphogenesis.

Importance

EP300 is relevant to: - Cancer research, due to its role in regulating oncogenes and tumour suppressor genes through acetylation - Neurodegenerative diseases, as it is implicated in processes like learning and memory through its influence on neuronal development - Metabolic disorders, given its involvement in fat cell differentiation and regulation of gluconeogenesis - Immune responses, particularly in T-helper cell differentiation and response to viral infections, highlighting its potential as a therapeutic target in immunology

Top Products

For researchers investigating EP300, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited Anti-KAT3B / p300 antibody [3G230 / NM-11] (ab14984), a monoclonal antibody that has garnered 90 citations, highlighting its reliability in Western blotting (WB) and chromatin immunoprecipitation (ChIP). Additionally, we offer the recombinant Anti-KAT3B / p300 antibody [EPR23495-268] (ab275378), which has been validated in knockout models and is suitable for a broader range of applications, including WB, ChIP, immunoprecipitation (IP), immunocytochemistry (ICC), and flow cytometry (FC). With 37 citations, this recombinant antibody is an excellent choice for researchers seeking consistency and versatility in their experiments. The Recombinant Human KAT3B / p300 protein ELISA Kit (ab56274) is an excellent option for researchers looking to study EP300 in their experiments.

Abcam Product Citation Summary

The data indicates that the EP300 target was investigated in the context of ACE2 regulation using human HuH7 cells. The use of western blotting suggests a focus on protein expression levels.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab275378
Human
WB
Regulation of ACE2
35231079

Domain

The CRD1 domain (cell cycle regulatory domain 1) mediates transcriptional repression of a subset of p300 responsive genes; it can be de-repressed by CDKN1A/p21WAF1 at least at some promoters. It contains sumoylation and acetylation sites and the same lysine residues may be targeted for the respective modifications. It is proposed that deacetylation by SIRT1 allows sumoylation leading to suppressed activity.

Function

Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling (PubMed:23415232, PubMed:23934153, PubMed:40240600, PubMed:8945521). Acetylates all four core histones in nucleosomes (PubMed:23415232, PubMed:23934153, PubMed:8945521). Histone acetylation gives an epigenetic tag for transcriptional activation (PubMed:23415232, PubMed:23934153, PubMed:8945521). 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 (PubMed:23415232). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905, PubMed:23911289). Also able to acetylate histone lysine residues that are already monomethylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Catalyzes formation of histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). In response to DNA damage, catalyzes acetylation of histone H1 at 'Lys-75' (H1K75ac) following histone H1 deamidation by CTPS1, increasing chromatin accessibility to facilitate the recruitment of DNA repair proteins (PubMed:40240600). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRDM16, PRMT1, SIRT2, STAT3, ZNF76 or GLUL (PubMed:12929931, PubMed:15653507, PubMed:16285960, PubMed:16337145, PubMed:16762839, PubMed:18722353, PubMed:18782771, PubMed:26990986). Acetylates 'Lys-131' of ALX1 and acts as its coactivator (PubMed:12929931). Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of p53/TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function (PubMed:18722353). Following DNA damage, forms a stress-responsive p53/TP53 coactivator complex with JMY which mediates p53/TP53 acetylation, thereby increasing p53/TP53-dependent transcription and apoptosis (PubMed:11511361, PubMed:15448695). Promotes chromatin acetylation in heat shock responsive HSP genes during the heat shock response (HSR), thereby stimulating HSR transcription (PubMed:18451878). 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 (PubMed:14752053). Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity (PubMed:15890677). Acetylates STAT3 at different sites, promoting both STAT3 dimerization and activation and recruitment to chromatin (PubMed:15653507, PubMed:16285960, PubMed:18782771). Acetylates BCL6 which 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 degradation, this mechanism may be involved in CD4/CD8 lineage differentiation (PubMed:20810990). Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (By similarity). Acetylates PCK1 and promotes PCK1 anaplerotic activity (PubMed:30193097). Acetylates RXRA and RXRG (PubMed:17761950). Acetylates isoform M2 of PKM (PKM2), promoting its homodimerization and conversion into a protein kinase (PubMed:24120661). Acetylates RPTOR in response to leucine, leading to activation of the mTORC1 complex (PubMed:30197302, PubMed:32561715). Acetylates RICTOR, leading to activation of the mTORC2 complex (PubMed:22084251). Mediates cAMP-gene regulation by binding specifically to phosphorylated CREBBP (PubMed:8917528). 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, propanoyl-CoA (propionyl-CoA) or isonicotinyl-CoA, and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation, propionylation or isonicotinylation, respectively (PubMed:17267393, PubMed:25818647, PubMed:29775581, PubMed:31645732, PubMed:34545082). 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).

(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.

Involvement in disease

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, intellectual disability 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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Cellular localization

Alternative names

P300, EP300, Histone acetyltransferase p300, p300 HAT, E1A-associated protein p300, Histone butyryltransferase p300, Histone crotonyltransferase p300, Protein 2-hydroxyisobutyryltransferase p300, Protein isonicotinyltransferase p300, Protein lactyltransferas p300, Protein propionyltransferase p300

swissprot:Q09472 omim:602700 entrezGene:2033

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