Title:

Epigenetic regulation and alteration in mouse spermatogenesis

 

Speaker:

So Maezawa

Professor, Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science

 

Abstract:

Germ cells are responsible for transmitting genetic information across generations through their differentiation into sperm or oocytes and reacquisition of totipotency after fertilization. This unique function requires the establishment of specialized epigenomic landscapes that regulate both germ cell differentiation and the activation of developmental gene programs.

Using the mouse model, we have investigated gene regulatory mechanisms during spermatogenesis and sought to elucidate the formation of germline-specific epigenomic features. Spermatogenesis involves a stepwise progression from undifferentiated spermatogonia through meiotic spermatocytes to haploid spermatids and mature sperm. This process is accompanied by large-scale, stage-specific shifts in gene expression, governed by dynamic epigenetic and chromatin structural changes. Importantly, some of the epigenetic marks established during spermatogenesis persist in sperm and may be transmitted to the next generation. Recent studies indicate that environmental factors such as aging and nutritional or psychological stress can alter the sperm epigenome, with potential intergenerational effects.

In this seminar, we will discuss our recent findings on the mechanisms of epigenomic regulation during spermatogenesis and highlight how environmental factors may induce epigenomic variability, contributing to heritable phenotypic outcomes.

 

 

Reference:

Maezawa S*, Yukawa M, Sakashita A, Barski A, Namekawa SH*. Site-specific DNA demethylation during spermatogenesis presets the sites of nucleosome retention in mouse sperm. eLife. 2025 Apr 9 105926.1.

Maezawa S*, Yukawa M, Hasegawa K, Sugiyama R, Iizuka M, Hu M, Sakashita A, Vidal M, Koseki H, Barski A, DeFalco T, and Namekawa SH*. PRC1 suppresses a female gene regulatory network to ensure testicular differentiation. Cell Death Dis. 2023 Aug 4;14(8):501.

Maezawa S*, Sakashita A, Yukawa M, Chen X, Takahashi K, Alavattam KG, Nakata I, Weirauch MT, Barski A, and Namekawa SH*. Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition. Nat Struct Mol Biol. 2020 Sep 7;27(10):978-988.

Maezawa S, Hasegawa K, Yukawa M, Kubo N, Sakashita A, Alavattam KG, Sin H, Kartashov AV, Sasaki H, Barski A, and Namekawa SH*. Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline. Proc Natl Acad Sci U S A. 2018 May 8;115(19):4957-4962.

Maezawa S, Hasegawa K, Yukawa M, Sakashita A, Alavattam KG, Andreassen PR, Vidal M, Koseki H, Barski A, and Namekawa SH*. Polycomb directs timely activation of germline genes in spermatogenesis. Genes Dev. 2017 Aug 15;31(16):1693-1703.