# Computational methods to identify neo-TADs and enhancer-hijacking in rearranged genomes

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $413,358

## Abstract

PROJECT SUMMARY / ABSTRACT
 Structural variations (SVs), including inversions, deletions, duplications, and translocations, are
prevalent in cancer and other diseases. It has been shown recently that SVs can disrupt the 3D genome
structure and directly contribute to pathogenesis. For example, in T-cell acute lymphoblastic leukemia, deletion
of a TAD boundary disrupted the insulated chromatin domains and activates proto-oncogenes. Two main
consequences of SVs on 3D genome structures are the formations of “neo-TADs” and “enhancer-hijacking.”
Neo-TADs refers to the scenarios when a SV event leads to the formation new chromatin domains, particularly
in the cancer genomes, while enhancer-hijacking means when a SV event rearranges the cancer genome and
juxtaposes an enhancer to the proximity of an oncogene.
 3D genome organization has been shown to be essential in proper gene regulation and cell fate.
Previous studies have shown that mammalian genomes are organized in megabase pair topologically
associating domains (TADs). Genes located within the same TADs tend to be co-regulated and the functions of
enhancers are usually restrained by TADs boundaries. Both genetic and epigenetic alteration of TADs
boundaries can lead to gene misregulation and severe human diseases. To study the 3D genome
organization, Hi-C is by far the most popular method, as it can measure chromatin interactions genome-wide. It
facilitates the original discovery of TADs and many enhancer-promoter interactions. Recently, Hi-C has been
applied to tens of cancer cell lines and a small number of patient samples. However, to our knowledge, no
methods exist that can identify neo-TADs or enhancer-hijacking events using the Hi-C interaction data in
cancer cells.
 Therefore, in this study, we propose the following aims: 1) Develop computational method to detect
neo-TADs in cancer genome; 2) Develop computational method to detect chromatin interactions in cancer
genomes; 3) Perform validation experiments for the hijacked enhancers by CRISPR/Cas9 and investigate
their effect on target genes and cell phenotypes.

## Key facts

- **NIH application ID:** 10235992
- **Project number:** 1R01HG011207-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Feng Yue
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $413,358
- **Award type:** 1
- **Project period:** 2021-06-07 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235992

## Citation

> US National Institutes of Health, RePORTER application 10235992, Computational methods to identify neo-TADs and enhancer-hijacking in rearranged genomes (1R01HG011207-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10235992. Licensed CC0.

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