# The tumor suppressive role of PBRM1, the bromodomain-containing subunit of the PBAF chromatin remodeling complex

> **NIH NIH U01** · PURDUE UNIVERSITY · 2020 · $349,196

## Abstract

Project Summary
Metastatic clear cell renal cell carcinoma (ccRCC) has low disease-free survival and limited therapeutic options.
The only treatments for ccRCC have been elucidated as a result of mechanistic understanding of tumor
suppression by VHL (von Hippel-Lindau), the most commonly mutated gene in ccRCC. After VHL, the second
most commonly mutated gene in ccRCC patients is Polybromo-1 (PBRM1), a subunit of the SWI/SNF (or BAF
for BRG1/BRM associated factors) chromatin remodeling complex, subunits of which are mutated in 20% of
human cancers. PBRM1 is characterized by six sequential bromodomains proposed to bind acetylated lysines
and is a subunit in a minor BAF subcomplex called PBAF (for Polybromo-1 BAF). The overall goal of this
proposal is to determine the mechanism of PBRM1-mediated chromatin targeting of the PBAF complex and
how that relates to downstream transcriptional regulation of genes important for tumor suppression in ccRCC.
Based on our preliminary data, we hypothesize that several of the six bromodomains of PBRM1 are required
for multivalent targeting of the PBAF complex to multiple histone acetylation sites located at genomic regions
important for the regulation of genes involved in cell adhesion and epithelial maintenance. In the proposed
study we plan to 1) Use cellular assays and animal models to confirm and characterize PBRM1 as a tumor
suppressor involved in the regulation of cell adhesion, 2) Define how PBRM1 status predicts therapeutic
efficacy of established and proposed ccRCC drugs, 3) Identify genomic binding sites for PBRM1 in ccRCC and
the transcriptional regulation by PBAF-mediated chromatin remodeling, and 4) Define the histone acetylation
marks responsible for specific recruitment of PBRM1 and PBAF. The proposed study will greatly increase our
understanding of the mechanisms involved in renal tumorigenesis and expand our understanding of the tumor
suppressive mechanisms of BAF-mediated chromatin remodeling. It is our belief that this study will provide
direct evidence of novel therapeutic targets for treating renal cancer.

## Key facts

- **NIH application ID:** 9908057
- **Project number:** 5U01CA207532-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Emily Carla Dykhuizen
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,196
- **Award type:** 5
- **Project period:** 2017-05-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908057

## Citation

> US National Institutes of Health, RePORTER application 9908057, The tumor suppressive role of PBRM1, the bromodomain-containing subunit of the PBAF chromatin remodeling complex (5U01CA207532-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908057. Licensed CC0.

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