# Biochemical Basis of Chromatin Folding and Chromosome Condensation

> **NIH NIH DP5** · NORTHWESTERN UNIVERSITY · 2020 · $395,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term goal of the PI’s research program is to elucidate the molecular mechanisms, structure, and
regulation of chromatin folding and chromosome condensation. The rationale for pursuing fundamental
investigations into DNA folding within nuclei and chromosomes is that this folding goes awry in a number of
human diseases, such as the congenital limb malformations brachydactyly, F-syndrome, and polydactyly, and
cancers such as glioma and T-cell acute lymphoblastic leukemia. Fundamental studies, such as those proposed
here, are needed to fully define the pathophysiology of these diseases and will serve as a basis for developing
specific, targeted therapeutics. In pursuit of this long-term goal, the objective during this project period is to
define DNA folding within topologically associating domains (TADs), recently discovered independently folded
domains of chromatin. TADs are regions of chromatin more likely to interact with themselves than with their
neighbors, and are up to 30-fold more condensed than a fully extended, “beads-on-a-string” chromatin fiber.
Specific aims for this project period are: (1) identify intrinsic properties of the chromatin fiber that affect TAD
folding, (2) elucidate the folding pattern of DNA within a TAD, and (3) elucidate how TAD structure changes as
cells enter mitosis. These aims will be attained using an innovative, holistic approach that integrates methods
from molecular genetics, molecular biology, cell biology, and genomics. The expected outcomes of this
combined approach is that completion of the proposed work will reveal how DNA is folded within TADs, and how
this folding changes as cells exit interphase and enter metaphase. These outcomes will have a positive impact
on the field of chromosome biology by providing a better molecular understanding of chromatin folding and
chromosome condensation. Such a molecular understanding is expected to ultimately reveal the impact of
chromatin folding on gene regulation and cellular heredity. This fundamental knowledge is necessary for defining
the pathophysiology of human disease and developing novel therapeutics.

## Key facts

- **NIH application ID:** 9993596
- **Project number:** 5DP5OD024587-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kyle Patrick Eagen
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993596

## Citation

> US National Institutes of Health, RePORTER application 9993596, Biochemical Basis of Chromatin Folding and Chromosome Condensation (5DP5OD024587-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993596. Licensed CC0.

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