# Understanding epigenetic remodeling in primordial germ cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $337,450

## Abstract

Summary
Germ cells are responsible for the passage of a parent's genome and epigenome from one generation to the
next. Although the genome does not change after fertilization (except in instances of DNA damage) the
epigenome in mammals is substantially altered through a process known as epigenetic remodeling. After
embryo implantation, a second major wave of epigenetic remodeling occurs, this time in newly specified germ
cells of the embryo called primordial germ cells (PGCs). The second wave of epigenetic remodeling, most
notably erasure of DNA methylation from the epigenome is speculated to erase any acquired epialleles that
could cause disease in future generations. In the last five years, my lab together with colleagues in the field
discovered that DNA methylation remodeling in mouse and human PGCs is incomplete, involving stage-
dependent combinations of DNA methylation erasure and DNA methylation protection. In our previous
funding period, we showed that disrupting stage-dependent DNA methylation remodeling in PGCs results in
germ cell loss and infertility. Given the importance of correctly staged DNA methylation remodeling to the
biology of PGCs and the ability to reproduce, we are next interested in the underlying chromatin landscape
responsible for dynamic DNA methylation protection and erasure. Results from this work will significantly
enhance our knowledge of the epigenetic basis of reproduction. In this renewal, our overall hypothesis is that
Polycomb repressor complex 2 upstream of Histone H3 Lysine 27 trimethylation (H3K27me3) (aim 1) and
Tripartite motif 28 (Trim28) upstream of H3K9me3 (aim 2) play major roles in stage-dependent DNA
methylation remodeling in PGCs. To address these hypotheses, we aim to use a combination of genomics,
epigenomics and mouse modeling. In addition, we also aim to use single cell sequencing technologies (aim 3)
to define the true epigenetic ground state of PGCs. In summary, identifying the epigenetic landscape of PGCs
and the enzymes required to maintain it are critical to prioritizing future studies that disrupt the epigenome in
PGCs during pregnancy, or the identification of epigenetic hot-spots in PGCs that could be tested for specific
roles in infertility or transgenerational epigenetic inheritance in the future.

## Key facts

- **NIH application ID:** 10148791
- **Project number:** 5R01HD058047-13
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Amander Clark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $337,450
- **Award type:** 5
- **Project period:** 2009-02-05 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148791

## Citation

> US National Institutes of Health, RePORTER application 10148791, Understanding epigenetic remodeling in primordial germ cells (5R01HD058047-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10148791. Licensed CC0.

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