# High throughput interrogation of non-coding variants and 3D genome organization

> **NIH NIH R35** · NORTHWESTERN UNIVERSITY · 2024 · $408,000

## Abstract

PROJECT SUMMARY / ABSTRACT
Recent large-scale efforts such as the ENCODE and Epigenome Roadmap projects have predicted millions of
potential non-coding regulatory elements in the human genome. However, it is not clear how many of them are
truly functional, as the predictions were mainly based on high-throughput genomics assays such as DNase-
Seq or ChIP-Seq for histone modifications and transcription factors. Most of the current studies indirectly
measure enhancer activity through transgenic reporter assays and therefore do not provide insights into the
native chromatin state. Fortunately, recent advances in high-throughput screening methods based on
CRISPR/Cas9 genome editing technology make such functional characterization possible. Another important
layer of gene regulation is the 3D genome organization, which can link the distal enhancers with their target
genes. High-throughput methods based on Chromatin Conformation Capture (3C) have emerged (such as Hi-
C, ChIA-PET, HiChIP, and Capture Hi-C) and present an unprecedented opportunity to study higher-order
chromatin structure genome-wide. Despite the recent advances, the complex relationship between chromatin
interactions and gene regulation has just begun to unravel. CTCF and cohesin complex have been shown to
be critical in the formation of chromatin loops and topologically associating domains (TADs), but we know little
of whether there are other important regulators are important for such chromatin interactions.
 Given the aforementioned challenges and my unique multi-disciplinary training, my long-term goal is to
use a combination of high throughput genomic experiments, computational modeling, and functional assays to
address the following two fundamental questions: 1) Identify functional enhancers through high-throughput
assays and study how genetic variants can affect their functions; 2) Identify novel regulators for the formation
of 3D genome organization features. The proposed work will deepen our understanding on how genetic
variants contribute to gene regulation, 3D genome organization, and molecular mechanisms underlying human
diseases.

## Key facts

- **NIH application ID:** 10915540
- **Project number:** 5R35GM124820-08
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Feng Yue
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $408,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915540

## Citation

> US National Institutes of Health, RePORTER application 10915540, High throughput interrogation of non-coding variants and 3D genome organization (5R35GM124820-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10915540. Licensed CC0.

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