EP300 Protein (p300)

EP300 Protein (p300)

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">EP300 Protein (p300)</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>EP300</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Histone Acetyltransferase p300</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q09472</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~264 kDa (2414 amino acids)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>HAT family (KAT3B)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous, high in brain, testis</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q13.2</td>
</tr>
<tr>
<td class="label">Transcription Factor</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">CREB</td>
<td>KIX domain</td>
</tr>
<tr>
<td class="label">[NF-κB](/entities/nf-kb)</td>
<td>CH1/CH3 domains</td>
</tr>
<tr>
<td class="label">p53</td>
<td>Multiple domains</td>
</tr>
<tr>
<td class="label">STATs</td>
<td>CH1 domain</td>
</tr>
<tr>
<td class="label">Nuclear receptors</td>
<td>NRID</td>
</tr>
<tr>
<td class="label">MyoD</td>
<td>CH3 domain</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">HAT activators</td>
<td>Increase histone acetylation</td>
</tr>
<tr>
<td class="label">HDAC inhibitors</td>
<td>Indirec

EP300 Protein (p300)

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">EP300 Protein (p300)</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>EP300</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Histone Acetyltransferase p300</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q09472</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~264 kDa (2414 amino acids)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>HAT family (KAT3B)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous, high in brain, testis</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q13.2</td>
</tr>
<tr>
<td class="label">Transcription Factor</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">CREB</td>
<td>KIX domain</td>
</tr>
<tr>
<td class="label">[NF-κB](/entities/nf-kb)</td>
<td>CH1/CH3 domains</td>
</tr>
<tr>
<td class="label">p53</td>
<td>Multiple domains</td>
</tr>
<tr>
<td class="label">STATs</td>
<td>CH1 domain</td>
</tr>
<tr>
<td class="label">Nuclear receptors</td>
<td>NRID</td>
</tr>
<tr>
<td class="label">MyoD</td>
<td>CH3 domain</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">HAT activators</td>
<td>Increase histone acetylation</td>
</tr>
<tr>
<td class="label">HDAC inhibitors</td>
<td>Indirect p300 activation</td>
</tr>
<tr>
<td class="label">CBP/p300-specific</td>
<td>Selective modulation</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Deliver functional p300</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">443 edges</a></td>
</tr>
</table>

Ep300 Protein (P300) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

EP300 (E1A-associated protein p300) is a transcriptional coactivator and histone acetyltransferase that plays a crucial role in regulating gene expression, cellular differentiation, and neuronal plasticity. p300 is one of the most important transcriptional coactivators in eukaryotes, with the ability to integrate signals from numerous transcription factors and chromatin remodeling complexes. It is essential for normal development, and mutations cause Rubinstein-Taybi syndrome in humans[@histone].

Protein Information

Protein Structure

The p300 protein contains multiple functional domains:

N-terminal Region

• Contains binding sites for numerous transcription factors
• Includes nuclear receptor interaction domain (NRID)
• Bromo domain for acetyl-lysine recognition

Histone Acetyltransferase (HAT) Domain

• Amino acids 1195-1673
• Catalyzes histone H3/H4 acetylation
• Central to coactivator function

Interacting Domains

• CH1/CH3: Transcriptional activator binding
• CH2: HAT domain support
• KIX: CREB and other transcription factor binding
• RING: E3 ubiquitin ligase activity
• ZZ: Zinc finger domain

Molecular Function

Histone Acetylation

p300 is a histone acetyltransferase (HAT) that[@pcbp]:

• Acetylates histone H3 (lysines 9, 14, 18, 27) and H4 (lysines 5, 8, 12, 16, 20)
• Opens chromatin structure, enabling transcription
• Creates binding sites for bromodomain-containing proteins
• Regulates nucleosome assembly

Transcriptional Coactivation

p300 serves as a molecular bridge:

Chromatin Remodeling

p300 recruits and coordinates:

• SWI/SNF complexes
• Mediator complex
• TFIID and other basal transcription factors
• Histone methyltransferases

Role in Neurodegeneration

Alzheimer's Disease

p300 dysfunction plays a significant role in AD[@alzheimers]:

• Reduced HAT activity: p300 activity decreased in AD brain
• Histone acetylation deficits: Global H3/H4 acetylation reduced
• Transcriptional dysregulation: Memory-related gene expression altered
• Amyloid-β effects: [Aβ](/proteins/amyloid-beta) inhibits p300 activity
• Therapeutic potential: [HDAC](/entities/hdac-enzymes) inhibitors boost p300/CBP function

Parkinson's Disease

In PD, p300 is implicated through[@parkinsons]:

• Dopaminergic signaling: p300 regulates tyrosine hydroxylase
• [α-Synuclein](/proteins/alpha-synuclein) toxicity: p300 modulates inclusion formation
• Neuroinflammation: NF-κB-p300 pathway in microglial activation
• Mitochondrial function: PGC-1α coactivation affected

Huntington's Disease

p300 in HD[@memory]:

• Transcriptional dysfunction: p300 activity altered by mutant [huntingtin](/proteins/huntingtin-protein)
• HAT inhibition: Reduced histone acetylation in HD models
• Therapeutic target: p300/CBP modulators in development

ALS

In ALS:

• Transcription regulation: p300 affects ALS-related genes
• RNA metabolism: Interactions with [TDP-43](/proteins/tdp-43) pathology
• Therapeutic approaches: HDAC inhibitors being investigated

Therapeutic Implications

Drug Development

Therapeutic Strategies

Animal Models

Knockout Studies

Conditional Knockouts

• Impaired learning and memory
• Reduced synaptic plasticity
• Altered gene expression
• Social behavior deficits

Transgenic Models

Research Directions

Key Publications

See Also

• [EP300 Gene](/proteins/ep300-protein)
• [CREBBP/CBP](/proteins/crebbp-protein)
• [Histone Acetylation](/mechanisms/histone-modification)
• [Epigenetic Therapy](/therapeutics/epigenetic-therapies-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Huntington's Disease](/diseases/huntington-disease)

External Links

• [NCBI Gene: EP300](https://www.ncbi.nlm.nih.gov/gene/2033)
• [UniProt: p300](https://www.uniprot.org/uniprot/Q09472)
• [Rubinstein-Taybi Syndrome Database](https://rubinstein-taybi.nature.com/)

Background

The study of Ep300 Protein (P300) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References