# Epigenetic inheritance of heterochromatin

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2024 · $371,205

## Abstract

Project Summary
The long-term goal of this work is to understand how histone H3 lysine 9 methylation (H3K9me) and
heterochromatic gene silencing are epigenetically inherited. Heterochromatin is a conserved feature of
eukaryotic chromosmes and plays important roles in regulation of gene expression and maintenance of
chromosome stability in organisms ranging from yeast to human. Using the fission yeast
Schiozosaccharomyces pombe as a model organism, we recently demonstrated that ectopically induced
domains of H3K9me and silencing can be epigenetically inherited in the absence of sequence-specific
recruitment when the rate of H3K9me demethylation is reduced by deletion of the Epe1 anti-silencing factor. In
addition, we have discovered that, in wildtype epe1+ cells, small noncoding RNAs (siRNAs) or transcription
factor binding sites play critical roles in epigenetic maintenance of H3K9me. More recently, we have
uncovered roles for an RNAi-independent RNA decay pathaway, autoregulation of the conserved histone
H3K9 methyltransferase, and core replication fork-associated proteins in epigenetic maintenance of
heterochromatin. In this proposal we will use a combination of in vivo approaches and biochemical assays to
investigate (1) the functions of a newly discovered RNA decay complex, called the rixosome, in epigenetic
inheritance, (2) the role of a replication fork-associated chromatin assembly complex in retention of histones
and epigenetic inheritance during DNA replication, and (3) the role of a conserved ubiquitin ligase in regulation
of H3K9 methylation and accurate heterochromatin formation. The ultimate goal of these studies is a
molecular understanding of the mechanisms that epigenetically maintain silent chromatin domains.

## Key facts

- **NIH application ID:** 10749063
- **Project number:** 5R01GM072805-19
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** DANESH MOAZED
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $371,205
- **Award type:** 5
- **Project period:** 2005-02-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749063

## Citation

> US National Institutes of Health, RePORTER application 10749063, Epigenetic inheritance of heterochromatin (5R01GM072805-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10749063. Licensed CC0.

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