# Bromodomain-containing Protein 4 in Profibrotic Gene Expression and Lung Fibrosis

> **NIH NIH R01** · OLD DOMINION UNIVERSITY · 2024 · $95,543

## Abstract

PROJECT SUMMARY
 Idiopathic pulmonary fibrosis (IPF) is a fatal lung disorder of unknown etiology. IPF is
characterized by altered epigenetic state. Epigenetic alterations are potentially reversible, thus
are attractive therapeutic targets. Chromatin structural remodeling through histone post-
translational-modifications control transcriptional responses. Acetylated histone marks as well as
some transcriptional factors are recognized by bromodomains (readers). Bromodomain-
containing protein (Brd) 4 is a member of the bromodomain and extraterminal (BET) family, which
binds to cell type-specific enhancers and promoters. Brd4 has been reported to be essential for
enhancer-mediated pro-fibrotic genes expression in many organ fibrosis. However mechanisms
of how Brd4 regulates genome-wide pro-fibrotic responses and its interaction with other his
acetyltransferase, such as p300, is not clear. Fibrotic responses involve many cellular processes,
including epigenetic alterations. Our preliminary data show that by blocking Brd4, multiple
profibrotic genes can be downregulated; inhibition of Brd4 can disrupt the association of p300 and
H3K27ac with profibrotic genes promoter region. We hypothesis that Brd4 affects chromatin
accessibility, mediates the up-regulation of profibrotic genes through interaction with p300 by
acetylating active enhancer mark H3K27ac during lung injury and repair process. Our aims are:
1. Determine the effects of Brd4 inhibition on profibrotic responses in lung fibroblasts; 2.
Determine if Brd4 through p300 mediates histone acetylation to regulate profibrotic genes
expression, 3. Determine the in vivo targeting of Brd4 inhibition in pre-clinical models of lung
fibrosis. Results from this research will make a significant impact on our understanding of the role
of Brd4 in epigenetic regulation in the pathobiology of IPF.

## Key facts

- **NIH application ID:** 11123766
- **Project number:** 6R01HL151702-05
- **Recipient organization:** OLD DOMINION UNIVERSITY
- **Principal Investigator:** Yan Sanders
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $95,543
- **Award type:** 6
- **Project period:** 2024-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11123766

## Citation

> US National Institutes of Health, RePORTER application 11123766, Bromodomain-containing Protein 4 in Profibrotic Gene Expression and Lung Fibrosis (6R01HL151702-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11123766. Licensed CC0.

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