# ATP-dependent and independent mechanisms of regulating chromatin states

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $794,894

## Abstract

Abstract
Chromatin provides a means to compartmentalize the genome into active (euchromatin) and heritably repressed
(heterochromatin) states. Changes in these states accompany changes in cellular differentiation and are
essential for stabilizing cellular identity. Both types of chromatin states are maintained and rearranged by the
combined action of diverse ATP-dependent chromatin remodeling motors and specific chromatin binding
proteins. The proposed work is aimed at studying the core mechanisms of some of the major
chromatin regulators to achieve a better understanding of how their activities are regulated in vivo. Using a
variety of biophysical approaches, we have uncovered that ATP-dependent remodelers use sophisticated auto-
inhibition based mechanisms. We have also uncovered hexasomes as the preferred substrate for one type of
conserved remodeler. These findings provide a biophysical basis for further probing why different remodelers
have different biological roles. We had previously discovered phase-separation behavior by HP1 proteins, the
core components of heterochromatin. Since then, we have uncovered that phase-separated heterochromatin
reconstituted in a test-tube possesses several of the biophysical properties attributed to heterochromatin in cells.
Here we will build on these new discoveries to ask the following questions:
1. Why are their differences in mechanism between remodelers from different classes?
2. How does action of remodelers at the nucleosome scale impact chromatin at bigger scales?
3. What is the role of phase-separation in heterochromatin regulation?

## Key facts

- **NIH application ID:** 10825533
- **Project number:** 5R35GM127020-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** GEETA J NARLIKAR
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $794,894
- **Award type:** 5
- **Project period:** 2018-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825533

## Citation

> US National Institutes of Health, RePORTER application 10825533, ATP-dependent and independent mechanisms of regulating chromatin states (5R35GM127020-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10825533. Licensed CC0.

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