# Determinants of genome-wide activity and specificity of SWI/SNF family chromatin remodeling

> **NIH NIH R35** · BAYLOR COLLEGE OF MEDICINE · 2024 · $400,000

## Abstract

Project Summary
Sequencing of genetic and epigenetic variants associated with disease states has revealed that ATP-
dependent chromatin remodelers are among the most frequently disrupted genes in a number of diseases. In
mammals, BAF (SWI/SNF), PBAF, and GBAF complexes are highly conserved ATP-dependent chromatin
remodelers that generate accessibility for DNA-templated processes. Although these complexes have well-
documented roles in many contexts, the mechanisms by which BAF-family complexes are regulated by specific
signals remains poorly understood. Additionally, accessible sites across the genome respond with extreme
heterogeneity to remodeling by these complexes, yet the basis of this heterogeneity, the physical origins of
remodeling specificity, as well as the effects on transcription after initiation remain largely unknown. Improved
understanding of these principles would provide powerful opportunities to manipulate gene expression in
normal and disease states. To address this challenge, we will develop and combine new tools in epigenetics,
chemical biology, and microscopy. We will make use of rapid technologies to manipulate BAF activity in living
cells using cell-permeable molecules, and measure the outcomes using sensitive, unbiased approaches,
including epigenomics and live-cell microscopy. We will use these tools to answer essential questions about
ATP-dependent chromatin remodeling specificity, including: (1) How are BAF (SWI/SNF) complexes regulated
via cellular signals? (2) Why do sites respond differently to chromatin remodeling? (3) How does chromatin
remodeling influence transcription after initiation? Revealing the fundamental mechanisms used by these
factors holds great promise to enable powerful intervention strategies for diverse human diseases.

## Key facts

- **NIH application ID:** 10844360
- **Project number:** 5R35GM137996-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Hamilton Courtney Hodges
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844360

## Citation

> US National Institutes of Health, RePORTER application 10844360, Determinants of genome-wide activity and specificity of SWI/SNF family chromatin remodeling (5R35GM137996-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10844360. Licensed CC0.

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