# Optogenomic mapping of chromatin accessibility in live cells

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $320,000

## Abstract

ABSTRACT
Physical access of DNA has been widely studied using multiple chromatin accessibility profiling methods,
including DNase-seq, ATAC-seq, MNase-seq and NOMe-seq. These studies have revealed the accessible
genome largely overlaps with cis- DNA regulatory elements such as enhancers and promoters, highlighting a
prominent role of chromatin-binding factors in establishing chromatin accessibility. However, recent chromatin
conformation imaging studies have suggested that higher-order chromatin organization can also impact
accessibility of DNA through packing. A pressing question is whether native chromatin packing conformation
regulates chromatin accessibility in living cells. The current technology is not suitable to resolve this issue
because of their technical limitations that alter the native configuration and biophysical features of higher-order
chromatin. Thus, our objective is to develop a new approach to quantitively measure chromatin accessibility
under native conditions in live cells. In this project, we will leverage the recently developed iLID-SspB optogenetic
module to design a light-controlled molecule probe for measuring the accessibility of local chromatin
conformation in live cells. In Aim 1, we will develop a pair of optically controlled chromatin accessibility probes,
composed of MNase-mClover3-SspB tracer and iLID-mRuby3-H2B anchor. Upon validation and optimization,
we will establish an experimental system that combine the optical genetic control with high throughput DNA
sequencing to probe the native accessible chromatin conformation. In Aim 2, we will apply this technology named
OMAC-seq (Optical Mapping of Accessible Chromatin using Sequencing) and develop a computational pipeline
to measure cell differentiation-coupled changes of chromatin conformation in live embryonic stem cells. In Aim
3, we will develop a mitosis-specific OMAC-seq toolkit to quantify accessible genome DNA in mitotic
chromosome. By completing these aims, the proposed OMAC-seq technology will be an enabling toolkit for
understanding the impact of higher order chromatin on genome accessibility.

## Key facts

- **NIH application ID:** 10911271
- **Project number:** 5R01GM149076-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** XIAOZHONG ALEC WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $320,000
- **Award type:** 5
- **Project period:** 2022-09-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911271

## Citation

> US National Institutes of Health, RePORTER application 10911271, Optogenomic mapping of chromatin accessibility in live cells (5R01GM149076-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10911271. Licensed CC0.

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