# Identifying mechanisms underpinning epigenetic homeostasis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $401,250

## Abstract

PROJECT SUMMARY
DNA methylation is important for gene regulation, transcriptional silencing of repetitive DNA and establishing
genomic imprinting. While DNA methylation is a dynamic modification, which is added and removed by writer
and eraser enzymes, it is faithfully inherited over many millions of cell divisions, and even evolutionary
timescales. How these writers and erasers combine to ensure such accurate epigenetic inheritance is a critical
question, as failure to accurately maintain DNA methylation patterns is associated with aging as well as
numerous diseases, including cancers. Despite the importance of DNA methylation writers and erasers, the
mechanisms that regulate and coordinate their genes to maintain epigenetic homeostasis remain poorly
understood. A major goal of the Williams lab is to eliminate this gap in knowledge. Using the epigenetic model
system Arabidopsis, which can tolerate loss-of-function mutations to all methylation writers and erasers, my lab
will perform a comprehensive study of the gene regulatory mechanisms that regulate the expression of writer
and eraser genes to ensure epigenetic homeostasis. This will include performing a mechanistic dissection of
the cell-cycle regulation of genes encoding writer and eraser enzymes and their targeting by anciently
conserved cell cycle transcription factors. Additionally, my lab seeks to identify new trans-acting factors
involved in the regulation of epigenetic homeostasis by studying a naturally occurring strain of Arabidopsis with
drastically different regulation of epigenetic modifiers. Lastly, my lab will precisely define how epigenetic
homeostasis is lost within some cells during aging, identifying mechanisms that contribute to age-dependent
DNA methylation losses, and determining how “epigenetic age” is influenced by organ regeneration and the
environment. Together, these approaches will generate multiple insights into how DNA methylation dynamics
are established at a cellular scale and coordinated to achieve epigenetic homeostasis. We anticipate that these
findings will provide new insights into the laws of epigenetic stability and inheritance, which are crucial for
understanding many aspects of the health of human cells.

## Key facts

- **NIH application ID:** 10938472
- **Project number:** 1R35GM154941-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Ben Williams
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $401,250
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938472

## Citation

> US National Institutes of Health, RePORTER application 10938472, Identifying mechanisms underpinning epigenetic homeostasis (1R35GM154941-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10938472. Licensed CC0.

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