# Renewal: MIRA: Epigenetic regulation of genome integrity, environmental interaction, and inheritance

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $427,625

## Abstract

PROJECT SUMMARY
Although the genome is a blueprint for making an organism, the epigenome (modification on the
genome without DNA sequence change) governs the functional outcome of genes and ultimately
shapes the organism. Epigenetic modification is a conserved and important gene regulatory mechanism
and plays quintessential roles in genome integrity, development, environmental responses, and
diseases. Despite the large number of correlative studies describing the altered modification patterns
in abnormal developmental and pathological tissues, whether they are a cause or a consequence is
poorly understood. This proposal dissects the molecular mechanism of epigenetic regulation and
functional consequences of epigenome perturbation under developmental and physiological conditions.
Specifically, we investigate i) how epigenome reprogramming in response to environmental cues might
lead to stress adaptation; ii) how an epigenetic switch regulates developmental phase transition; and
iii) how epigenetic modification safeguards the genome integrity. We will further dissect the causal roles
of epigenetic marks on gene expression and develop an innovative CRISPR/Cas9-mediated cis-
engineering system for epigenome editing. Our approach is highly interdisciplinary making use of the
powerful Arabidopsis genetic system, high-throughput proteomics and genomics, live-cell imaging
techniques, biochemical and structural tools to tackle mechanistic problems from genome-wide scale
to atomic resolution. As we probe basic principles governing epigenetic regulation that are conserved
across eukaryotes, the mechanistic knowledge and epigenome technologies acquired from our
pioneering Arabidopsis studies will help accelerate progress in deciphering the relevant mechanisms in
human. Such knowledge will lead to the development of innovative tools to correct aberrant epigenetic
modifications and ultimately enable new applications for medicine and human health.

## Key facts

- **NIH application ID:** 10884427
- **Project number:** 5R35GM124806-08
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** XUEHUA ZHONG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,625
- **Award type:** 5
- **Project period:** 2017-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884427

## Citation

> US National Institutes of Health, RePORTER application 10884427, Renewal: MIRA: Epigenetic regulation of genome integrity, environmental interaction, and inheritance (5R35GM124806-08). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10884427. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*