# Regulation of Chromatin by Phase Separation

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $65,310

## Abstract

Project Summary
 Transcription and genome organization play important roles in cellular signaling, where both can
amplify and reinforce cancer-specific gene expression. While significant advances have been made in
understanding how chromatin is organized within the nucleus, the exact mechanisms mammalian cells use to
organize their genome both in normal cells as well as in cancer remains unclear. Many cellular structures have
recently been found to be phase separated bodies known as biomolecular condensates. Biomolecular
condensates are membrane-less sub-organellar bodies driven to form by constituents with multivalent
architecture. These condensates concentrate particular molecular constituents, altering their localization and
biochemical activities in cells. The nucleolus, heterochromatin foci, and PML bodies are all nuclear
biomolecular condensates, but whether any other micron-scale nuclear structures are similarly organized
remains to be seen. Using biochemical, cell biological, and genomic approaches, the research proposed here
aims to understand the portions of the genome undergo phase separation, focusing in particular on the
“enhancer” regions that direct gene expression in cancer cells. Through two specific aims, the proposed
experiments will (1) determine the molecular components necessary to promote phase separation of
chromatin, as well as (2) elucidate the contribution of multivalent proteins BRD4 and BRD4-NUT to oncogenic
phase separation of chromatin at super- and mega-enhancers. This proposed research should advance
understanding of nuclear organization, specifically addressing how phase separation might contribute to gene
expression control in cancer cells. Moreover, the work proposed here may uncover new therapeutic strategies
for cancer, focused on approaches that modulate phase separation and genome organization in the nucleus.

## Key facts

- **NIH application ID:** 9911981
- **Project number:** 5F32GM129925-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Bryan A Gibson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2018-11-16 → 2021-03-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9911981

## Citation

> US National Institutes of Health, RePORTER application 9911981, Regulation of Chromatin by Phase Separation (5F32GM129925-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9911981. Licensed CC0.

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