# Epigenetic gene regulation in the germline

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $20,320

## Abstract

One of the greatest mysteries in biology concerns how life has perpetuated, and continues to 
perpetuate, from generation to generation. A key feature of the mammalian germline is 
its sexual dimorphism: spermatogenesis and oogenesis. These dimorphic developmental 
processes are inherently complex, and this complexity poses significant challenges to 
understanding the perpetuity of life and the development of treatments for various germline-derived 
genetic and epigenetic diseases. Thus, in this R35 application, our research directions converge 
to address the following question: How do epigenetic mechanisms govern distinct sexually 
dimorphic processes in spermatogenesis and oogenesis, culminating in the generation of functional 
sperm and eggs? Since I became independent ten years ago, I and my team have worked to construct 
 a detailed picture of the epigenetic mechanisms that govern mammalian spermatogenesis. We 
have shown that the mitosis-to-meiosis transition in germ cell development is notable for not only 
global changes in gene expression but the dynamic reorganization of the epigenome; in brief, we 
have revealed that meiosis itself is a process of global epigenomic reprogramming. My research 
program has pioneered these concepts and developed innovative approaches to decode germline 
mechanisms crucial for preparing the next generation, providing a rigorous foundation for future 
research.
To understand key sexually dimorphic processes, we focus on fundamental 
processes in spermatogenesis and oogenesis. In spermatogenesis, postnatal germ cells enter a stem 
cell stage, undergo meiosis, and sustain long-term production of sperm. We will elucidate the 
global epigenetic mechanisms underlying spermatogenesis from the stem cell stage to sperm 
production, with an emphasis on dynamic changes in the epigenetic machinery and their 
importance to the next generation. Since, in males, meiotic sex chromosome inactivation (MSCI) 
functions as a key sexually dimorphic process, we will also determine the molecular functions of 
DNA damage response pathways-which direct MSCl-in the epigenetic regulation of the sex chromosomes. 
In contrast, female germ cells undergo meiosis in embryos and enter a prolonged stage of 
meiotic arrest-spanning decades in humans-prior to oocyte maturation. We will determine 
epigenetic mechanisms underlying critical stages of oogenesis to complement our study of 
male germ cells. Ultimately, we will reveal distinct features and unifying principles of 
spermatogenesis and oogenesis. Taking all of this together, we are uniquely positioned to clarify 
how fundamental germline mechanisms intersect to ensure genome maintenance, genome defense, and 
epigenetic gene regulation on a systemic level. The research directions proposed in this 
application are cohesive and synergistic, with high potential to sustain research 
progress and inform significant, transformative advances in germline biology, human 
reproduction, and repr...

## Key facts

- **NIH application ID:** 11089654
- **Project number:** 3R35GM141085-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Satoshi Namekawa
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $20,320
- **Award type:** 3
- **Project period:** 2021-07-05 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11089654

## Citation

> US National Institutes of Health, RePORTER application 11089654, Epigenetic gene regulation in the germline (3R35GM141085-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11089654. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*