# Dissecting the Dynamic Interplay Between, p53, Chromatin and Transcriptional Bursting in Single Cells

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $346,080

## Abstract

Project Summary
Mammalian gene expression is a stochastic process marked by short periods (minutes) of intense activity or
bursts of transcription interspersed between long intervals (>30 minutes to hours) of inactivity. Many genes
also display transcriptional memory (TM), where an initial stimuli primes a promoter subsequently allowing
faster and stronger re-activation of gene expression. TM can occur over both long (cell-divisions/LTTM) and
short (hours/STTM) timescales. Mechanisms regulating mammalian STTM and its relationship to
transcriptional bursting are poorly understood. This knowledge is critical for understanding how this process
becomes dysregulated in diseases such as cancer. Our live cell imaging system will survey the molecular
origins of the multiple ON states of bursting and transcriptional noise suppression that lead to STTM at a large
cohort of genes.
Preliminary data show 1.) transcription from the endogenous p21 and ACTB loci displays multi-phasic bursting
(MPTB) associated with different burst durations and Pol II initiation rates 2.) multi-phasic bursting patterns
exhibit STTM which can be modulated up and down via different stimuli. 3.) Noise is inversely correlated with
STTM and is suppressed via histone methylation. Our long-term goal is to understand how gene expression is
coordinately controlled by chromatin to restrict or grant of access of transcription factors to target promoters.
Based on our preliminary data and previous studies, we hypothesize that MPTB and STTM arise from the
coordinated recruitment of alternative pre-initiation complexes.
This hypothesis will be tested using cutting-edge single molecule live-cell microscopy in the following 3 specific
aims: 1.) Define the molecular origins of Multi-Phasic Transcriptional Bursting (MPTB). Live cell imaging will
determine the relationship between alternative pre-initiation complexes and the different burst states. 2.) Define
how Short-term transcriptional memory (STTM) is related to MPTB and the DNA damage response. Live cell
imaging will determine the prevalence of STTM at a large cohort of genes and the molecular mechanism of
how MPTB and STTM is regulated during the DNA damage response. 3.) Define the relationship between
transcriptional noise, MPTB, and STTM. Live-cell imaging will be used to determine how noise modulators
impact MPTB and STTM. These studies will provide key insights into how transcriptional bursting and STTM is
modulated by the dynamic interplay between activators, pre-initiation factors, and Pol II.

## Key facts

- **NIH application ID:** 10892848
- **Project number:** 5R01GM126045-08
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Robert Coleman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $346,080
- **Award type:** 5
- **Project period:** 2018-04-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892848

## Citation

> US National Institutes of Health, RePORTER application 10892848, Dissecting the Dynamic Interplay Between, p53, Chromatin and Transcriptional Bursting in Single Cells (5R01GM126045-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10892848. Licensed CC0.

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