# Epigenetic Inheritance of Heterochromatin

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $360,154

## Abstract

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. In the fission yeast
Schiozosaccharomyces pombe, the establishment of heterochromatin involves RNAi- and transcription
factor-dependent recruitment mechanisms, but the mechanisms that mediate epigenetic inheritance,
independently of the initial recruitment signals, have remained unclear. 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 demethylase. 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. In
this proposal we will use a combination of in vivo approaches and biochemical assays to investigate (1)
the functions of a newly discovered complex as well as known histone chapernones in epigenetic
inheritance and the transfer of parental histones to newly replicated DNA, (2) the mechanism of siRNA-
mediated epigenetic inheritance, and (3) the role of DNA sequence- and chromosomal context-
dependent mechanisms in cis maintenance of epigenetic states. The ultimate goal of these studies is a
molecular understanding of the mechanisms that epigenetically maintain silent chromatin domains.

## Key facts

- **NIH application ID:** 9959440
- **Project number:** 5R01GM072805-16
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** DANESH MOAZED
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $360,154
- **Award type:** 5
- **Project period:** 2005-02-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959440

## Citation

> US National Institutes of Health, RePORTER application 9959440, Epigenetic Inheritance of Heterochromatin (5R01GM072805-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9959440. Licensed CC0.

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