# Development of Single Molecule Chromatin Interaction Assays (smChIA) in Single Nuclei

> **NIH NIH R01** · JACKSON LABORATORY · 2020 · $567,427

## Abstract

PROJECT SUMMARY
The current 3D genome mapping technologies (including ChIA-PET and Hi-C) require millions of cells for each
assay and primarily rely on proximity ligation, PCR amplification of the ligation products, and Illumina-based high
throughput sequencing. While such methods have revealed many principles of chromatin interaction and useful
3D genome organizational maps based on signals averaged over millions of cells, they provided only binary
(paired) chromatin contact information, and thus do not enable elucidating the precise molecular mechanisms of
complex chromatin interactions occurring in individual cells. The development of single-cell 3D genome mapping
technologies has thus attracted significant interest in the research community. However, current single cell
strategies are still largely based on the conventional molecular approaches for DNA manipulation mentioned
above, which present technical barriers that prevent true single-molecule and single cell analyses genome-wide.
In this project, we propose to develop a completely new system of next generation technology for chromatin
interaction assays based on the SeqLL single-molecule protein-detection and DNA-sequencing platform. A
prototype single-molecule platform has been demonstrated for simultaneous detection of histone modifications
and genomic positions of individual nucleosomes (Shema et al., 2016). We will adapt this platform to enable
single-molecule Chromatin Interaction Analysis (smChIA) in single nuclei. The proposed smChIA method
possesses several important advantages over the current methods, including single-molecule resolution in single
nuclei, no need of PCR or any amplification, and most significantly the elimination of proximity ligation steps. To
aggressively advance the development of this next generation chromatin interaction analysis technology, we
have assembled an integrative team with interdisciplinary and complementary knowledge and skills to ensure
successful implementation of the specific aims in the proposal. We have also established an academic-industry
partnership to make quick dissemination of the technology to the larger research community. Our preliminary
results have provided initial proof-of-concept for the strategy of smChIA. We believe smChIA has the potential
to revolutionize the entire field of 3D genome biology from data acquisition to interpretation. Once fully developed,
we expect that the smChIA data will generate exciting and novel biological insights in the organization of the 3D
genome and its dynamic modulation.

## Key facts

- **NIH application ID:** 9857045
- **Project number:** 5R01GM127531-02
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Chia-Lin Wei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $567,427
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857045

## Citation

> US National Institutes of Health, RePORTER application 9857045, Development of Single Molecule Chromatin Interaction Assays (smChIA) in Single Nuclei (5R01GM127531-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857045. Licensed CC0.

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