EP300 Antibodies

Background

The EP300 gene encodes a highly conserved histone acetyltransferase, which is mainly present in the nucleus of eukaryotes. This protein is widely involved in chromatin remodeling and gene transcriptional regulation by catalyzing the acetylation modification of histones and other transcription-related proteins, thereby influencing important biological processes such as cell proliferation, differentiation and DNA damage repair. Since its identification in the early 1990s, EP300 has continuously attracted attention due to its crucial role in cell signal integration and tumorigenesis. Related research has not only revealed its functions in embryonic development and immune regulation, but also promoted a deeper understanding of epigenetic mechanisms and cancer therapeutic targets.

Structure Function Application Advantage Our Products

Structure of EP300

EP300 is a large multifunctional protein with a molecular weight of approximately 300 kDa. Its molecular weight is highly conserved across different species, which is mainly attributed to its highly conserved domain composition.

Species	Human	Mouse	Zebrafish	Fruit fly
Molecular Weight (kDa)	~300	~300	~290	~280
Primary Structural Differences	HAT domain (acetyltransferase activity), BROMO domain (recognition of acetylated lysine), CH domain (binding to CREB/c-Fos), and multiple protein interaction domains	Highly homologous to humans, with a highly conserved core domain	The core catalytic domain is conserved and participates in the regulation of early development	The homologous gene is CBP and has a similar HAT and protein-protein interaction domain

This protein is composed of 2,414 amino acids, and its functional core lies in its modular domain composition. The nuclear localization signal at the N-terminal of the protein guides it into the nucleus. The key histone acetyltransferase domain is responsible for catalyzing lysine acetylation at the histone tail, thereby opening up the chromatin structure. Adjacent bromine domains can specifically recognize and bind to acetylated histone markers, forming positive feedback regulation. In addition, the multiple protein-interacting domains it contains, such as CH1 and CH3, enable it to serve as a vast "hub" of transcriptional co-activators, integrating transcription factors from various signaling pathways including CREB, p53, and HIF-1α, and coordinating complex gene expression programs.

Fig. 1 Structure prediction of the complex of CREBBP mutations.¹

Key structural properties of EP300:

Modular multi-functional domain composition
Core histone acetyltransferase (HAT) catalytic domain
Bromine structure domain responsible for identifying acetylated histone marks
Multiple protein-interacting domains (such as CH1 and CH3) integrate transcription factor signals
Internal disorder district mediated phase separation and transcription condensed matter form

Functions of EP300

The main function of the EP300 protein (also known as p300) is to act as a transcriptional co-activator and histone acetyltransferase. However, it is also widely involved in a variety of cellular processes, including cell cycle regulation, DNA damage repair and cell differentiation.

Function	Description
Transcriptional regulation	By acetylating histones (such as H3K27ac), the chromatin structure is relaxed, creating conditions for the recruitment of transcription factors and RNA polymerases, thereby activating gene expression.
Signal path integration	As a "molecular hub" for multiple signaling pathways, it binds to hundreds of transcription factors such as p53, CREB, HIF-1α, and NF-κB through its multiple protein-protein interaction domains, coordinating complex gene expression programs.
Cell differentiation and development	It is crucial for embryonic development, especially playing a core role in the formation of the heart, nervous system and hematopoietic system. The deficiency of its function can lead to serious developmental defects.
DNA damage repair	It participates in the repair process of DNA double-strand breaks and promotes the assembly of damage recognition and repair complexes by acetylating repaid-related proteins (such as p53 and Ku70).
Tumor suppression and oncogenes	Mutations or abnormal expression exist in various cancers, and its function is dual: it exerts tumor suppressor effects by activating tumor suppressor genes (such as p53), but sometimes it also promotes tumor occurrence due to abnormal activation of proto-oncogenes.

Unlike a single enzymatic catalytic function, the EP300 is more like a large transcriptional "signal processor". Its histone acetyltransferase activity provides the basic chromatin environment for gene activation, and its dynamic and synergistic interaction with numerous transcription factors enables it to precisely respond to and integrate different upstream signals, thereby determining the expression timing and intensity of specific genes. This makes it the core regulator of cell fate determination and homeostasis maintenance.

Applications of EP300 and EP300 Antibody in Literature

1. Nicosia, Luciano, et al. "Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies." Cancer Cell 41.12 (2023): 2136-2153. https://doi.org/10.1016/j.ccell.2023.11.001

The novel inhibitor CCS1477 targets the bromine domain of EP300/CBP, which can drive it away from oncogenic enhancers (such as the MYB site in AML and the IRF4 site in myeloma) and reposition it near differentiation genes. Thus, it can induce leukemia differentiation and objective remission of myeloma in preclinical and early clinical trials, demonstrating potential for synergistic treatment.

2. Rubio, Karla, et al. "EP300 as a molecular integrator of fibrotic transcriptional programs." International Journal of Molecular Sciences 24.15 (2023): 12302. https://doi.org/10.3390/ijms241512302

The article indicates that EP300, as a key histone acetyltransferase, drives the process of multi-organ fibrosis by regulating chromatin structure and gene expression. Inhibiting EP300 can reduce extracellular matrix deposition, inflammation and epithelial-mesenchymal transition, providing a new target direction for anti-fibrotic therapy.

3. Emmons, Michael F., et al. "HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis." Nature communications 14.1 (2023): 7759. https://doi.org/10.1038/s41467-023-43519-1

Research has found that stress-induced HDAC8 promotes brain metastasis by inactivating EP300 and driving melanoma to transform into a neural crest stem cell-like state. This reveals a new direction for regulating tumor heterogeneity by targeting the HDAC8-EP300 axis.

4. Huang, Yao-Hui, et al. "CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis." Signal transduction and targeted therapy 6.1 (2021): 10. https://doi.org/10.1038/s41392-020-00437-8

Research has found that in diffuse large B-cell lymphoma, CREBBP/EP300 gene mutations inhibit the expression of FBXW7 by reducing the acetylation level of H3K27, thereby activating the NOTCH pathway, promoting the polarization of M2-type tumor-associated macrophages and accelerating tumor progression.

5. Tauziède-Espariat, Arnault, et al. "CNS tumor with EP300:: BCOR fusion: discussing its prevalence in adult population." Acta neuropathologica communications 11.1 (2023): 26. https://doi.org/10.1186/s40478-023-01523-y

The study reported two cases of adult central nervous system tumors carrying the EP300::BCOR fusion gene. This type of tumor differs from the internal tandem repeat type of BCOR in terms of age, location and BCOR protein expression, and may be included in the future WHO classification criteria.

Creative Biolabs: EP300 Antibodies for Research

Creative Biolabs specializes in the production of high-quality EP300 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom EP300 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our EP300 antibodies, custom preparations, or technical support, contact us at email.

Reference

Huang, Yao-Hui, et al. "CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis." Signal transduction and targeted therapy 6.1 (2021): 10. https://doi.org/10.1038/s41392-020-00437-8