# The function of H3K23me3, a transgenerationally inherited heterochromatin mark

> **NIH NIH F30** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $42,505

## Abstract

PROJECT SUMMARY:
H3K23 methylation is an evolutionarily conserved but understudied heterochromatic histone modification
whose function is unknown. In the past year our lab used C. elegans to study H3K23 methylation and found
that it plays a role in nuclear RNAi. Nuclear RNAi is an evolutionarily conserved pathway in which small
interfering RNAs (siRNAs) guide chromatin modifications and transcriptional repression. It protects the host
genome by epigenetically silencing transposons and other “non-self” DNA. We have made the following
discoveries: (1) H3K23me3 is induced by nuclear RNAi and is inherited for four generations. (2) The histone
methyltransferase SET-32, methylates H3K23 in vitro. (3) Both set-32 and the nuclear RNAi effector protein,
hrde-1, are required for nuclear RNAi-induced H3K23me3 in vivo. These discoveries have raised new
questions. What are the other histone methyltransferases responsible for H3K23me3? What is the function of
H3K23me3? Could H3K23me3 contribute to transcriptional silencing in nuclear RNAi? In this proposal I will
take genetic, biochemical, and computational approaches to address these questions in the following aims. (1)
Biochemically characterize and identify the histone methyltransferase(s) responsible for this modification. (2)
Create a functional knockout of H3K23me3 using a dominant negative mutation first discovered in cancer. (3)
Study the function of H3K23me3 in nuclear RNAi. The proposed studies, which explore a fundamental yet
unmapped territory of modern biology, will advance our understanding of the histone code, histone
methyltransferases, oncogenic histones, RNA-mediated transcriptional silencing, and RNA-chromatin
interaction, which are all relevant to human development and disease.

## Key facts

- **NIH application ID:** 10155982
- **Project number:** 1F30GM134578-01A1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** LIANNA SCHWARTZ-ORBACH
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $42,505
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155982

## Citation

> US National Institutes of Health, RePORTER application 10155982, The function of H3K23me3, a transgenerationally inherited heterochromatin mark (1F30GM134578-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155982. Licensed CC0.

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