# Three Dimensional Chromosome Architecture in Drug Addiction

> **NIH NIH DP1** · FLORIDA STATE UNIVERSITY · 2021 · $462,000

## Abstract

PROJECT SUMMARY / ABSTRACT
Neural function requires accurate control of gene transcription in response to environmental stimuli.
Aberrant gene expression is believed to drive drug addiction. Therefore, studying the regulation of gene
expression in drug addiction may provide mechanistic insights to this disease, which still offers limited
options for treatment and represents a vast social and economic burden. It is estimated that there are up to
one million regulatory elements in the mammalian genome, which are often located great distances from
their target genes. Although recent developments in next generation sequencing have provided large-scale
identification of regulatory DNA elements, which genes they regulate remains largely unknown. Recently,
the ordered compaction and organization of linear DNA into the nucleus has been recognized as having a
major influence on gene transcription by facilitating interactions between gene promoters and distal
regulatory elements. However, how this three-dimensional chromatin architecture is organized in the brain
and how it is changed, particularly in drug addiction, is still obscure. Here we propose to study the long-
range looping interactions between distal DNA elements and all annotated mouse gene promoters within
the specific neuronal subtypes differentially engaged in addiction. To achieve this, we will apply the cutting
edge promoter capture Hi-C technology to profile the entire promoter interactome in D1- and D2- medium
spiny neurons (MSNs) in nucleus accumbens, the key brain reward structure. We will also examine the
neuron subtype-specific higher order genome organization in both cocaine and heroin addicted mice. We
anticipate to elucidate neuron subtype specific and drug specific three-dimensional chromosome
architecture changes. Many of these changes may involve previously identified genetic variation sites
conserved between rodents and human. Manipulation of these regulatory regions may not only alter
regulation of their target gene's expression, but may also change the associated addiction behaviors. Upon
completion, our study will not only indisputably advance our understanding of drug addiction to the
unachieved dimension of genome architecture organization, it will also open a new avenue to a plausible
manipulation of the disease, which has potential utility for future therapeutic applications.

## Key facts

- **NIH application ID:** 10159232
- **Project number:** 5DP1DA046587-04
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Jian Feng
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $462,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159232

## Citation

> US National Institutes of Health, RePORTER application 10159232, Three Dimensional Chromosome Architecture in Drug Addiction (5DP1DA046587-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10159232. Licensed CC0.

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