NDLI: DPPA3 facilitates genome-wide DNA demethylation in mouse primordial germ cells

Content Provider	Springer Nature : BioMed Central
Author	Toriyama, Keisuke Au Yeung, Wan Kin Inoue, Azusa Kurimoto, Kazuki Yabuta, Yukihiro Saitou, Mitinori Nakamura, Toshinobu Nakano, Toru Sasaki, Hiroyuki
Abstract	Background Genome-wide DNA demethylation occurs in mammalian primordial germ cells (PGCs) as part of the epigenetic reprogramming important for gametogenesis and resetting the epigenetic information for totipotency. Dppa3 (also known as Stella or Pgc7) is highly expressed in mouse PGCs and oocytes and encodes a factor essential for female fertility. It prevents excessive DNA methylation in oocytes and ensures proper gene expression in preimplantation embryos: however, its role in PGCs is largely unexplored. In the present study, we investigated whether or not DPPA3 has an impact on CG methylation/demethylation in mouse PGCs. Results We show that DPPA3 plays a role in genome-wide demethylation in PGCs even before sex differentiation. Dppa3 knockout female PGCs show aberrant hypermethylation, most predominantly at H3K9me3-marked retrotransposons, which persists up to the fully-grown oocyte stage. DPPA3 works downstream of PRDM14, a master regulator of epigenetic reprogramming in embryonic stem cells and PGCs, and independently of TET1, an enzyme that hydroxylates 5-methylcytosine. Conclusions The results suggest that DPPA3 facilitates DNA demethylation through a replication-coupled passive mechanism in PGCs. Our study identifies DPPA3 as a novel epigenetic reprogramming factor in mouse PGCs.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-024-10192-7.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-024-10192-7
Journal	BMC Genomics
Issue Number	1
Volume Number	25
Language	English
Publisher	BioMed Central
Publisher Date	2024-04-05
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Stella Dppa3 Prdm14 Tet1 Primordial germ cell DNA demethylation Epigenetic reprogramming
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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