# Mechanisms of formation of 3D genome structures

> **NIH NIH DP5** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2020 · $485,000

## Abstract

Abstract
 Three dimensional genome organization is emerging as a potent regulator of gene expression. Due to
recent advancements in methods used to study higher-order chromatin structure, there has been a dramatic
increase in the understanding of how the human genome is organized in three dimensional space. This has
led to a greater appreciation for the role of 3D genome architecture in regulating nuclear biology, and a
recognition of the role of alterations to normal 3D genome structure in causing human disease. Despite this,
the mechanisms used by cells to build higher-order chromatin structures remain relatively obscure. The
experiments in this proposal will shed light on the mechanisms of higher-order chromatin structure formation
using two primary approaches. First, how cells construct their own 3D genome architectures will be studied by
taking advantage of naturally occurring biological systems where chromatin structures are formed and re-
formed. This will be accomplished by studying changes that occur during re-formation of chromatin structure
after exit from mitosis, and by studying the formation of new chromatin loops in the genome upon change in
cellular identity. Second, to determine how higher-order chromatin structures are built, CRISPR/Cas9
technology will be used to engineer exogenous chromatin loops into the genome. This will be accomplished by
delivering protein cargo using Cas9 fusion proteins to specific loci in the genome to perform locus specific “re-
programming.” This will be used to assess what are the minimal essential events that are required to create
higher-order chromatin structures in the genome. These experiments will greatly expand our knowledge of the
mechanisms used to construct higher-order chromatin structures in our genome and will provide the necessary
foundation to link our knowledge of 3D genome organization to human phenotypic variation and disease.

## Key facts

- **NIH application ID:** 9989924
- **Project number:** 5DP5OD023071-05
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Jesse R Dixon
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,000
- **Award type:** 5
- **Project period:** 2016-09-16 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989924

## Citation

> US National Institutes of Health, RePORTER application 9989924, Mechanisms of formation of 3D genome structures (5DP5OD023071-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989924. Licensed CC0.

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