# Regulation of chromatin folding in space and time

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2020 · $402,500

## Abstract

Abstract
 Eukaryotic genomes encode genetic information in their linear sequence, but appropriate expression of
their genes requires chromosomes to fold into complex and spatially distinct three-dimensional structures.
Recent advances in genomic-based approaches have uncovered a hierarchy of DNA interactions, from small
chromatin loops that connect genes and enhancers to larger chromosomal domains and nuclear
compartments. However, despite the remarkable conservation of these organizational features and their
impact on gene function, we have a very limited understanding of how chromosomes are spatially partitioned,
functionally packaged, and relatively positioned in the nucleus. Technical limitations have also hindered our
ability to ask questions regarding cell-to-cell variability and the relationship between chromatin folding,
positioning, and function at single cell resolution.
 Our previous studies involved the development of two technologies that use fluorescent in situ
hybridization (FISH) to interrogate chromosome positioning at single-cell resolution. Our goal is to build on this
work and use these tools to elucidate how chromosomal segments find each other and then form stable
interactions within cells. I can envision three immediate stages for our work. The first is developing a rapid and
precise method for identifying candidates involved in chromosome interactions. The second is establishing a
battery of in situ-based assays that can be used to characterize the candidates, and the third is translating our
findings from model organisms to humans. Collectively, the studies proposed here will uncover novel molecular
mechanisms underlying nuclear organization, providing a new avenue to study how chromatin folding and
positioning is established and inherited, and how dysfunctional organization contributes to disease.

## Key facts

- **NIH application ID:** 9942479
- **Project number:** 5R35GM128903-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Eric F. Joyce
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942479

## Citation

> US National Institutes of Health, RePORTER application 9942479, Regulation of chromatin folding in space and time (5R35GM128903-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9942479. Licensed CC0.

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