# The Role of BRD4 in Cardiac Specification

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $402,500

## Abstract

Summary Statement
Cardiovascular disease remains the leading cause of death in the United States. One emerging long-term
strategy for patients with congestive heart failure focuses on cellular regeneration. Efforts include boosting the
function of existing cardiac myocytes, introducing immature myocytes into failing hearts, and even introducing
electrically insulated patches of myocardium. All of these efforts require a highly-detailed understanding of the
molecular determinants that drive myocyte lineage specification and differentiation and the mechanistic basis
by which these factors regulate lineage specific gene expression cascades. Landmark studies have revealed a
critical role for the Bromodomain extraterminal domain (BET) protein Brd4 in regulating lineage specific gene
programs by recognizing or reading areas of the genome marked by specific modifications. In addition, studies
abrogating BET protein function in murine models of heart failure have demonstrated promising results, by
modulating lineage specific function. However, the normal role of BET proteins, specifically Brd4, has not been
elucidated during cardiac development. Our data implicates a critical role for Brd4 during cardiac development,
specifically by transcriptionally activating genes poised for expression upon lineage adoption. We seek to
define the exact programs activated by Brd4 during cardiac development. In addition, our studies seek to
understand if cardiac progenitor cells are rendered vulnerable to adopting aberrant cell fates upon loss of
activation cues (via loss of Brd4). Our work will provide essential insight into how Brd4 drives cardiac lineage
specification, ultimately allowing for manipulation of this process to generate cell types of interest. Defining the
molecular pathways which regulate myogenesis will undoubtedly shape emerging novel therapeutics and
regenerative strategi

## Key facts

- **NIH application ID:** 9856459
- **Project number:** 5R01HL139783-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Rajan Jain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856459

## Citation

> US National Institutes of Health, RePORTER application 9856459, The Role of BRD4 in Cardiac Specification (5R01HL139783-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856459. Licensed CC0.

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