# Control of early germline development in C. elegans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $502,691

## Abstract

Project Summary/Abstract
The long-term objective of my research program is to understand how epigenetic information is transmitted
across generations and during development. Epigenetic mechanisms enable gene expression and
development to be regulated not only by DNA sequence but also by how DNA is packaged into chromatin.
The mechanisms for faithfully transmitting information via chromatin packaging or the “epigenome” through
DNA replication to daughter cells and from parents to offspring remain mysterious. My lab has developed a
powerful model for investigating those mechanisms. In the nematode Caenorhabditis elegans, a set of
histone-modifying enzymes enables the parental chromosomes inherited by embryos to transmit an
epigenetic “memory of germline” from parent germ cells to the primordial germ cells (PGCs) in offspring.
Germ cells that do not inherit that memory die. The key players are MES-4, which marks transcribed
regions of the genome with an ON mark (methylation of histone H3 on Lys 36 or H3K36me), and Polycomb
Repressive Complex 2 or PRC2, which marks repressed regions of the genome with an OFF mark
(H3K27me). Our working hypothesis is that 1) MES-4 and PRC2 mark genomic regions as transcribed
(ON) or repressed (OFF) in the parental germline, 2) that pattern of ON and OFF marking is passed to
offspring via oocyte and sperm chromatin, and 3) maternally provided MES-4 and PRC2 propagate the
pattern through cell divisions to provide the PGCs with proper gene expression “blueprints” for germline
development. Our aims test key aspects of this hypothesis. In Aim 1, we will determine if the sperm and
oocyte epigenomes each transmit a “memory of germline” to offspring. We will elucidate the distributions of
critical histone marks on the sperm and oocyte genomes, the fates of specific sperm and oocyte marking
patterns in early embryonic cells, and the consequences of altered sperm or oocyte marking to germline
development in offspring. In Aim 2, we will determine how marked and unmarked chromatin states are
faithfully propagated through cell divisions by targeted MES-4 and PRC2 action. In Aim 3, we will test if
MES-4 and PRC2 marking in parents regulates the transcription program in PGCs, and if altering
transcription in the parental germline, by exposing parent worms to environment stresses, leads to altered
chromatin marking and transcription patterns in offspring.
Epidemiological studies of human populations suggest that what parents experience can affect the
physiology, health, and lifespan of their offspring and even grand-offspring. The germline is the conduit
between generations. Our studies, which lie at the heart of transgenerational epigenetic inheritance, will
provide critical insights into germ cell biology, how chromatin states transmit information from parents to
offspring, and how parental experiences may influence the health and longevity of future generations.

## Key facts

- **NIH application ID:** 9975858
- **Project number:** 5R01GM034059-34
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Susan Strome
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $502,691
- **Award type:** 5
- **Project period:** 1984-09-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975858

## Citation

> US National Institutes of Health, RePORTER application 9975858, Control of early germline development in C. elegans (5R01GM034059-34). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975858. Licensed CC0.

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