# Regulation of chromosome structure and gene expression by architectural proteins

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $386,074

## Abstract

PROJECT SUMMARY
 The spatial organization of DNA within the nucleus is critical for proper gene expression and cellular
function. Patterns of genome folding can vary by cell type and are perturbed in human diseases such as
developmental syndromes and cancers. The molecular mechanisms that govern genome organization are
poorly understood and yet are critically important for human health.
 A hierarchy of structures link genome topology and activity. Critical structures for gene control are the
chromatin loops that bring genes and their regulatory elements together in close physical proximity. Genome-
wide profiling indicates that there are more than 10 regulatory elements for every gene, yet little is known about
how regulatory elements find their target genes or how they function at the molecular level. A major goal in the
field is to identify all of the DNA loops in the genome and determine how they act individually and in
combination to regulate gene expression.
 The Structural Maintenance of Chromosome (SMC) complexes are a family of proteins that play key roles in
shaping the three-dimensional architecture of the genome. The two major SMC complexes, Cohesin and
Condensin, were first identified for their roles in chromosome re-organization during the cell cycle. Recent
work has implicated these factors in gene regulation during interphase, and the assumption is that these ring-
shaped protein complexes act by facilitating loops in DNA. It is important to uncover the mechanisms that
determine where and how Cohesin and Condensin interact with the genome and the functional consequences
of these loop structures to development and disease processes.
 The long-term scope of this research program is to move from a linear view of the genome to a panoramic
view where the physical orientation of the genome in three-dimensional space directs gene expression. This
project will focus on three major questions. First, what does each architectural protein contribute to the overall
topology of the genome? Second, how are architectural proteins regulated during DNA looping and gene
regulation? Third, how do DNA loops impact gene activity? These studies will assess the biochemical and
molecular processes that control gene expression and DNA looping and determine the consequences of
specific mutant architectural proteins. This research will shed light on how regulatory elements control genome
organization, direct gene expression, and define cell types during development.

## Key facts

- **NIH application ID:** 10225486
- **Project number:** 5R35GM124764-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jill Dowen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,074
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225486

## Citation

> US National Institutes of Health, RePORTER application 10225486, Regulation of chromosome structure and gene expression by architectural proteins (5R35GM124764-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225486. Licensed CC0.

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