bims-mazytr 2025-07-13 papers

Issue of 2025–07–13
five papers selected by
川一刀

Cell Genom. 2025 Jul 09. pii: S2666-979X(25)00178-8. [Epub ahead of print]5(7): 100922

Peripheral chromatin remodeling at the center of zygotic genome activation.

Pal and colleagues1 investigate the molecular regulation of LAD establishment in mouse preimplantation embryos. This study provides insights into the physiological remodeling of LADs, revealing that zygotic LADs may be, in fact, dispensable during the very early steps of mouse development when they can be rescued at the 2-cell stage.

DOI: https://doi.org/10.1016/j.xgen.2025.100922

PLoS Biol. 2025 Jul;23(7): e3003239

H3K4me2 distinguishes a distinct class of enhancers during the maternal-to-zygotic transition.

Matthew D Hurton, Jennifer M Miller, Miler T Lee.

After egg fertilization, an initially silent embryonic genome is transcriptionally activated during the maternal-to-zygotic transition. In zebrafish, maternal vertebrate pluripotency factors Nanog, Pou5f3 (OCT4 homolog), and Sox19b (SOX2 homolog) (NPS) play essential roles in orchestrating embryonic genome activation, acting as "pioneers" that open condensed chromatin and mediate acquisition of activating histone modifications. However, some embryonic gene transcription still occurs in the absence of these factors, suggesting the existence of other mechanisms regulating genome activation. To identify chromatin signatures of these unknown pathways, we profiled the histone modification landscape of zebrafish embryos using CUT&RUN. Our regulatory map revealed two subclasses of enhancers distinguished by presence or absence of H3K4me2. Enhancers lacking H3K4me2 tend to require NPS factors for de novo activation, while enhancers bearing H3K4me2 are epigenetically bookmarked by DNA hypomethylation to recapitulate gamete activity in the embryo, independent of NPS pioneering. Thus, parallel enhancer activation pathways combine to induce transcriptional reprogramming to pluripotency in the early embryo.

DOI: https://doi.org/10.1371/journal.pbio.3003239

bioRxiv. 2025 Jul 06. pii: 2025.07.06.663377. [Epub ahead of print]

An Epigenomic Roadmap Primes Non-Growing Oocytes for Maturation and Early Embryogenesis.

Mengwen Hu, Yasuhisa Munakata, Yu-Han Yeh, Han Wang, Neil Hunter, Richard M Schultz, Satoshi H Namekawa.

Female reproductive lifespan is defined by long-lived, non-growing oocytes (NGOs) that comprise the ovarian reserve. NGOs are assumed to acquire the epigenetic marks that will define the early embryo only after they exit the ovarian reserve and become activated for growth. Contrary to this dogma, we show that mouse NGOs possess abundant histone modifications that both underlie maintenance of the ovarian reserve and prime the epigenome of growing oocytes for early embryogenesis. As NGOs are established around birth, Polycomb Repressive Complex 1 (PRC1) mediates abundant H2AK119 ubiquitylation and reprograms the H3K27 acetylation landscape, which is essential to maintain the ovarian reserve. Importantly, the PRC1-driven epigenetic state of NGOs provides a blueprint for subsequent generation of a PRC2-catalyzed H3K27 trimethylation profile in growing oocytes that is characterized by broad domains and DNA methylation-independent imprints that are transmitted to the embryo. Thus, Polycomb complexes play pivotal roles in priming the NGO epigenome for oocyte maturation and early embryogenesis.

DOI: https://doi.org/10.1101/2025.07.06.663377

Matern Fetal Med. 2025 Apr;7(2): 85-94

Alternative Splicing in Embryo Implantation.

Luping Yu, Sijing Zhu, Haili Bao, Shuangbo Kong.

Alternative splicing (AS) is a crucial process that produces functionally distinct proteins from a single gene, depending on the developmental or physiological state of cells in multicellular organisms. It plays a significant role in cellular proliferation, survival, and differentiation, including embryonic development, spermatogenesis, and a broad spectrum of diseases. However, the precise involvement of AS in embryo implantation is still unclear. In this review, we summarize the potential roles of AS in regulating mesenchymal-epithelial transitions during embryo implantation, specifically in epithelium regeneration and decidualization initiation via the mesenchymal-epithelial transformation process. Overall, this review emphasizes the impact of AS and splicing variants on embryo implantation and offers novel insights into the potential application of alternative splicing in the treatment of female infertility.

Keywords: EMT/MET; Embryo implantation; Spliceosome; Splicing

DOI: https://doi.org/10.1097/FM9.0000000000000272

J Vis Exp. 2025 Jun 17.

Stable Isotope In-Vivo Labeling for Mass-Spectrometry Identification of Paternal Metabolites Transferred from Sperm to Oocyte During Fertilization.

Luca Roberto, Gilda Cobellis, Concetta Ambrosino, Pietro Campiglia, Mariano Stornaiuolo.

Paternal contribution to embryo genetics has so far been limited to allelic sequences for decades. A decade of results suggests, instead, that epigenetic factors-DNA methylation, histone modifications, chromosomal organization, and regulatory RNAs-play crucial roles in paternal inheritance and influence embryonic development and zygote gene expression. Together with nucleic acids, sperm metabolome (lipids, carbohydrates, free amino acids) may act as epigenetic signal. This protocol aims to identify sperm-to-oocyte transferred metabolites by mass spectrometry. The procedure includes stable isotope labeling of sperm cells with 2H2O or U13C Glucose to trace, by metabolomics, paternal metabolites transferred to the oocyte during fertilization. The overall goal of the protocol is to reveal the role of paternal sperm metabolome in offspring's susceptibility to dysmetabolism, and it may be adapted to provide insights into how environmental conditions, such as diet and exposure to pollutants, alter paternal metabolic messages, potentially affecting offspring's health and predisposition to diabetes, obesity, and cardiovascular diseases.

DOI: https://doi.org/10.3791/67765