# Chromatin Domain Structure and Function

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $379,991

## Abstract

Increasing genomic and cytological evidence suggests that where a gene is located within the nucleus
and how it is folded within the interphase chromosome may produce comparable increases in a gene's
transcriptional output as the initial binding of transcription factors to promoter sequences. Our long-term goals
are to determine the intranuclear positioning and large-scale chromatin structure of specific gene loci, to
identify the cis and trans determinants of this positioning and folding, and to determine the functional
significance of this level of chromatin organization. Our hypothesis is that gene positioning and large-scale
chromatin folding create a global chromatin environment whose influence on transcriptional regulation of
certain genes is quantitatively is at least as large as the influence of local cis regulatory elements. Our goals for
the next funding period will be to: 1) develop a new genomic method for measuring actual large-scale
chromatin compaction; 2) determine the functional connections between gene positioning to the nuclear
lamina and speckles and large-scale chromatin compaction with gene regulation; 3) dissect the relationships
between large-scale chromatin folding, chromatin domain epigenetic states, and nuclear compartmentalization
with each other and with transcriptional regulation. This work builds on several key advances during the last
funding period, including: a) Development of our novel TSA-Seq method for genome-wide mapping of
intranuclear gene positioning; b) Demonstration of deterministic positioning of >50% of the most highly
expressed genes near nuclear speckles; c) Demonstration of long-range, directed movement of Hsp70
transgenes loci to nuclear speckles upon heat-shock; d) Demonstration of a tight correlation between speckle
association and full Hsp70 transgene activation; e) Reconstitution of large chromatin domains with distinct
nuclear compartmentalization, epigenetic, and large-scale chromatin condensation states and identification of
cis and trans factors which determine these states.
 Together these advances enable this proposal's unique “Divide-and-Conquer” experimental approach
in which we identify trans factors regulating gene positioning and/or large-scale chromatin compaction of
particular gene loci and then use genomic methods to survey the genome-wide relevance of these trans
factors to gene positioning, large-scale chromatin compaction, and gene regulation. Through this research we
will gain a better understanding of gene regulation and how to manipulate gene expression for possible future
therapeutic approaches.

## Key facts

- **NIH application ID:** 10098327
- **Project number:** 5R01GM058460-20
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Andrew Steven Belmont
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,991
- **Award type:** 5
- **Project period:** 1999-02-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098327

## Citation

> US National Institutes of Health, RePORTER application 10098327, Chromatin Domain Structure and Function (5R01GM058460-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10098327. Licensed CC0.

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