# Identification and analysis of non-coding loci critical for cell viability and chromatin organization

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $587,485

## Abstract

Project Summary:
The effort to identify functional non-coding sequences has largely focused on the regulatory elements such as
enhancers and non-coding RNAs. However, while ~70% of the human genome is epigenetically quiescent, i.e.
not marked by any epigenetic modification indicating functional inactivity, the majority of somatic mutations
associated with diseases occur in the non-coding regions. An emerging question is why and how somatic
mutations in epigenetically quiescent loci would affect cellular functions and cause disease formation. A
possible mechanism is that the mutations in these loci may alter the neighbor chromatin organization and such
a change is propagated through the 3D genome to generate a profound impact on phenotype. Although this
hypothesis is tempting, such non-coding loci have not been widely identified, characterized and analyzed in the
human genome. In the proposed work, we aim to integrate computational prediction and CRISPR library
screen to systematically uncover non-coding loci that do not host any functional element and are not even
marked by histone modification, protein binding or open chromatin but are important for cell survival (Specific
Aim 1 and 2). We will investigate the mechanisms of how the deletion of these loci lead to cell dysfunction
using Hi-C, single cell RNA-seq and single ATAC-seq analyses (Specific Aim 3). Once completed, the
proposed work will provide a new aspect of understanding the functions of epigenetically quiescent non-coding
loci and facilitate developing genome-editing based therapeutics targeting these loci.

## Key facts

- **NIH application ID:** 10834258
- **Project number:** 5R01HG009626-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Wei Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $587,485
- **Award type:** 5
- **Project period:** 2017-06-03 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834258

## Citation

> US National Institutes of Health, RePORTER application 10834258, Identification and analysis of non-coding loci critical for cell viability and chromatin organization (5R01HG009626-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10834258. Licensed CC0.

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