# Structural and Functional Analysis of the Chd1 Chromatin Remodeler

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $404,221

## Abstract

ABSTRACT
 Chromatin remodelers are ATP-dependent DNA translocases that catalyze disassembly, reassembly, and
repositioning of nucleosomes throughout eukaryotic genomes. As evidenced from multiple types of cancer and
developmental disorders associated with remodeler inactivation, chromatin remodeling is essential for normal
growth and development. Remodeling requires transient and controlled disruption of histone-DNA interactions,
with different families of remodelers possessing unique domains thought to assist or regulate action of a
conserved ATPase motor. Our crystal structure of the Chd1 chromatin remodeler provided the first view of
ATPase motor regulation, showing how a DNA-binding surface of the ATPase motor was blocked by adjacent
chromodomains. As seen from work with the ISWI remodeler family, the auto-inhibitory nature of the Chd1
chromodomains has proven to be a common strategy for regulating ATPase action on the nucleosome.
However, it remains unclear how such domain-domain interactions enable remodelers to sense and respond to
particular nucleosome substrates, or achieve unique remodeling outcomes. Here we follow up our recent
discoveries of Chd1 architecture on the nucleosome, where the Chd1 DNA-binding domain was found to
directly communicate with the chromo-ATPase across the gyres of the nucleosome. We propose to test the
hypothesis that inter-domain interactions of Chd1 are responsible for sensing DNA outside the nucleosome
and that domains work together to achieve particular remodeling outcomes.
 In addition to remodeler regulation, the mechanism by which chromatin remodelers reposition nucleosomes
along DNA is also poorly understood. Intriguing single molecule FRET experiments with the ISWI remodeler
have revealed step-like and discontinuous movements DNA, suggesting that DNA behaves as a spring on the
nucleosome. We will test this idea and further investigate DNA interactions needed for high processive steps
that we also observe for Chd1. Together, these studies will provide new mechanistic insights into how
chromatin remodelers manipulate the structure of the nucleosome and use domain-domain communication to
regulate remodeler action.
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## Key facts

- **NIH application ID:** 9912780
- **Project number:** 5R01GM084192-13
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** GREGORY DEAN BOWMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,221
- **Award type:** 5
- **Project period:** 2008-04-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912780

## Citation

> US National Institutes of Health, RePORTER application 9912780, Structural and Functional Analysis of the Chd1 Chromatin Remodeler (5R01GM084192-13). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9912780. Licensed CC0.

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