# Epigenetic Regulation of Gene Expression during Spermatogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $314,000

## Abstract

ABSTRACT
The goal of this study is to elucidate the epigenetic mechanisms underlying dynamic genome-wide
gene expression during spermatogenesis. The gene expression program of germ cells is distinct from that
of somatic lineages. Importantly, the somatic gene expression program is largely suppressed in male germ
cells. Instead, male germ cells retain a unique cellular identity that is passed on to sperm and gives rise to a
totipotent zygote after fertilization. Our recent RNA-seq analysis showed that about three thousand
spermatogenesis-specific genes are activated, while approximately three thousand genes expressed in both
somatic lineages and progenitor cells of the male germline (termed somatic/progenitor genes) are largely
suppressed during late spermatogenesis, i.e., in meiosis and in postmeiotic spermatids. We identified SCML2
as the suppressor of somatic/progenitor genes. SCML2 is a germline-specific subunit of the Polycomb
repressive complex 1 (PRC1), a regulator of heritable gene repression during development. We have
discovered that Polycomb complexes determine the gene expression profile by programming genes for both
repression and activation. Our combined results suggest that the epigenome of undifferentiated spermatogonia
is preset (termed “preprogrammed”) both for subsequent genome-wide gene silencing and activation during
spermatogenesis (termed “programmed differentiation”). What remain unknown are the mechanisms whereby
Polycomb proteins regulate gene expression during spermatogenesis. Our central hypothesis is that
Polycomb proteins cooperate to preprogram the epigenome in undifferentiated spermatogonia, thus
regulating the subsequent dynamic genome-wide expression profile and programmed differentiation
necessary for spermatogenesis. This study will address how the epigenome of undifferentiated
spermatogonia is prepared to respond to differentiation cues and, afterwards, how the differentiation program
is maintained through mitotic and meiotic divisions. We have designed two complementary specific aims. In
Aim 1, we will elucidate how PRC1 defines heritable gene activation and silencing during spermatogenesis. In
Aim 2, we will address how SCML2 preprograms the epigenome for later spermatogenic differentiation. These
studies will reveal novel epigenetic mechanisms by which interplay between Polycomb proteins regulates the
dynamic gene expression during spermatogenesis.

## Key facts

- **NIH application ID:** 10292862
- **Project number:** 7R01GM122776-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Satoshi Namekawa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $314,000
- **Award type:** 7
- **Project period:** 2018-01-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292862

## Citation

> US National Institutes of Health, RePORTER application 10292862, Epigenetic Regulation of Gene Expression during Spermatogenesis (7R01GM122776-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10292862. Licensed CC0.

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