# Heterochromatin in the developing vertebrate embryo

> **NIH NIH R35** · UNIVERSITY OF GEORGIA · 2021 · $377,500

## Abstract

Project Summary:
Segregation of DNA into open euchromatin and more condensed heterochromatin is fundamental to eukaryotic
genome organization. Chromatin accessibility influences cell-fate choice in development and its dysregulation
is common in disease. While the presence of euchromatic and heterochromatic compartments has been
appreciated for over a century, we still know almost nothing about the mechanisms that drive the initial, rapid
fractionation of genomes into these distinct domains during embryogenesis. Moreover, although we and others
have shown that the large-scale de novo establishment of heterochromatin is tightly linked to the onset of
zygotic gene expression in animals, the transcriptional consequences of accelerating or delaying
heterochromatin establishment during this early window of vertebrate development are not known. My
laboratory focuses on Histone H3 lysine 9 trimethyl (H3K9me3) marked heterochromatin, which forms the
major blocks of heterochromatin in vertebrates. H3K9me3 marked heterochromatin is required for the silencing
of transposons, suppression of inappropriate recombination, proper chromosome segregation and appropriate
transcription of developmentally important genes. Here, we propose an innovative program combining genetic,
genomic and molecular biology approaches, which seeks to uncover the mechanisms that control the large-
scale de novo establishment of H3K9me3 marked heterochromatin during early vertebrate embryogenesis and
to define the consequences of shifting the timing of heterochromatin establishment in the embryo. We choose
zebrafish as a model because there are clear parallels between heterochromatin regulation in zebrafish and in
mammals, and because external fertilization of the zebrafish embryo facilitates the molecular interrogation of
chromatin in very early development. Over the course of our studies, we will elucidate the functions of several
newly identified regulators of heterochromatin establishment, test requirements for zygotic transcripts in
directing de novo heterochromatin formation and clarify the relationship between 5-methylcytosine and
H3K9me3 in early embryogenesis. We will also identify early developmental programs that are impacted by
altering the timeline of heterochromatin establishment in the embryo. This research is significant, as it
addresses critical and long-standing knowledge gaps in our understanding of heterochromatin formation and
function during early vertebrate embryogenesis. Understanding how heterochromatin is first established during
development, and its functions in regulating early transcription is necessary for us to understand how
heterochromatin misregulation contributes to disease, and how we might intervene to reset aberrant chromatin
states using targeted therapies.

## Key facts

- **NIH application ID:** 10086280
- **Project number:** 1R35GM139556-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Mary Grace Goll
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,500
- **Award type:** 1
- **Project period:** 2021-08-13 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086280

## Citation

> US National Institutes of Health, RePORTER application 10086280, Heterochromatin in the developing vertebrate embryo (1R35GM139556-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10086280. Licensed CC0.

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