# Epigenetic mechanisms for regulation of p300

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $444,380

## Abstract

Project Summary
 Human p300 is a transcriptional co-activator and a major acetyltransferase that acetylates
histones and other proteins, facilitating gene transcription. P300 is required for a wide array of
cellular programs, including cell growth, differentiation, apoptosis, and DNA repair, and is
implicated in human diseases, cancer and genetic disorders in particular. P300 and its paralog
CBP are among the most frequently mutated genes in human malignancies. p300 contains a
unique assembly of the catalytic histone acetyltransferase (HAT) domain closely linked to the ZZ
domain, the biological role of which remains unclear. We have identified the ZZ domain of p300
(ZZp300) as a novel epigenetic reader that recognizes histone H3 tail. Our findings suggest that
this recognition mediates catalytic and chromatin binding activities of p300. The molecular
mechanisms and functional significance of these novel p300 activities are unknown and are the
focus of the proposed studies.
 We hypothesize that the interaction of ZZp300 with H3 promotes selective acetylation of the
histone H3K27 and H3K18 sites by p300. Furthermore, we propose that ZZp300 cooperates with
bromodomain (BDp300) in the recruitment and stabilization of p300 at chromatin. We will employ a
powerful combination of in vitro and in vivo approaches to establish the molecular and structural
basis, mechanistic insights, and biological significance of crosstalk between histone readers in
p300. This research is of fundamental importance to our understanding of the physiological and
pathogenic activities of p300. These studies will also shed light on the role of the novel epigenetic
reader, ZZp300, allowing us to build a model of signaling by this major acetyltransferase, and will
lead to a better understanding of human diseases associated with aberrant p300 activity, including
cancer and genetic disorders.

## Key facts

- **NIH application ID:** 9872740
- **Project number:** 1R01GM135671-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** TATIANA G KUTATELADZE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $444,380
- **Award type:** 1
- **Project period:** 2020-01-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872740

## Citation

> US National Institutes of Health, RePORTER application 9872740, Epigenetic mechanisms for regulation of p300 (1R01GM135671-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872740. Licensed CC0.

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