# Mechanisms and Consequences of Specific Chromatin Arrangements in vivo

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2020 · $307,800

## Abstract

Project Summary/Abstract
Chromatin structure is a major determinant of eukaryotic gene expression, and the regulation of chromatin is a
fundamental step in all dynamic cellular responses. Improper regulation of chromatin leads to developmental
defects and human cancers. The overall goal of this project is to understand how dynamic changes in
chromatin structure are encoded in a static genome, and determine how these changes are orchestrated in a
condition-specific manner. To begin to achieve this goal, we are modeling condition-specific establishment of
nucleosome positions by a transcription factor-targeted chromatin remodeling protein. While sequence-specific
transcription factors are widely known to recruit and interact with chromatin remodeling machinery, how these
interactions regulate nucleosome positioning outcomes is largely undetermined. Recent studies have shown
that Ume6-recruited ISW2 complex leads to highly precise motif-proximal nucleosome positioning. The
mechanism of these specific chromatin remodeling events will be dissected using a combination of
biochemistry and genomics to answer the following three fundamental questions: 1) How does Ume6
interaction with ISW2 lead to motif-proximal nucleosome selection at Ume6 targets. 2) How is the final
nucleosome position achieved through Ume6-ISW2 interactions and ISW2 autoregulation. 3) How do motif-
proximal nucleosome positions at Ume6 targets affect transcriptional repression. Answering these questions is
critical to elucidating how specific chromatin segments are rearranged in a predictable manner, and will provide
a conceptual framework through which condition-specific sequence-targeted chromatin remodeling events can
be understood.

## Key facts

- **NIH application ID:** 9969385
- **Project number:** 5R01GM129242-03
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Laura Emily McKnight
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $307,800
- **Award type:** 5
- **Project period:** 2018-07-11 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969385

## Citation

> US National Institutes of Health, RePORTER application 9969385, Mechanisms and Consequences of Specific Chromatin Arrangements in vivo (5R01GM129242-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969385. Licensed CC0.

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