Epigenetic reprogramming in mouse primordial germ cells.

By P. Hájková, S. Erhardt, Natasha Lane, T. Haaf, O. El-Maarri, Wolf Reik, Jörn Walter, M. Surani. Mechanisms of Development, 2002

1,241 citations recorded by the source corpus.

Genome-wide epigenetic reprogramming in mammalian germ cells, zygote and early embryos, plays a crucial role in regulating genome functions at critical stages of development. We show here that mouse primordial germ cells (PGCs) exhibit dynamic changes in epigenetic modifications between days 10.5 and 12.5 post coitum (dpc). First, contrary to previous suggestions, we show that PGCs do indeed acquire genome-wide de novo methylation during early development and migration into the genital ridge. However, following their entry into the genital ridge, there is rapid erasure of DNA methylation of regions within imprinted and non-imprinted loci. For most genes, the erasure commences simultaneously in PGCs in both male and female embryos, which is completed within 1 day of development. Based on the kinetics of this process, we suggest that this is an active demethylation process initiated upon the entry of PGCs into the gonadal anlagen. The timing of reprogramming in PGCs is crucial since it ensures that germ cells of both sexes acquire an equivalent epigenetic state prior to the differentiation of the definitive male and female germ cells in which new parental imprints are established subsequently. Some repetitive elements, however, show incomplete erasure, which may be essential for chromosome stability and for preventing activation of transposons to reduce the risk of germline mutations. Aberrant epigenetic reprogramming in the germ line would cause the inheritance of epimutations that may have consequences for human diseases as suggested by studies on mouse models.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/74b869463f0a4d858ddc97c94d4317206440f3ed

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Yi Zhang
2. Wolf Reik
3. Hao Wu
4. A. Bird
5. W. Dean
6. Jörn Walter
7. R. Jaenisch
8. Frederica Perera

In Molecular Biology

1. Yi Zhang
2. Hao Wu
3. Wolf Reik
4. A. Bird
5. W. Dean
6. Jörn Walter
7. Tom Misteli
8. R. Jaenisch

Citations in the corpus

• Epigenetic reprogramming in mammals. (2005, background): “Secondly, some retrotransposon families seem relatively resistant to demethylation compared to the rest of the genome, in both PGCs and zygotes (21,70).”
• Nutrition and epigenetics: An interplay of dietary methyl donors, one-carbon metabolism, and DNA methylation (2012, neutral): “These reprogramming events throughout the life course result in tissue-specific DNA methylation patterning [2,13].”
• DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos (2014, background): “This reprogramming process also reverses other somatic epigenetic features: Parental imprints are erased (Hajkova et al. 2002; Sasaki and Matsui 2008), and the silenced X chromosome is reactivated in PGCs of female mouse embryos (Chuva de Sousa Lopes et al.”
• The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells (2012, background): “…sequences analyzed by bisulfite sequencing, including some differentially methylated regions (DMRs) in imprinted genes, were demethylated relatively late once PGCs were colonizing the gonads (Hajkova et al., 2002; Lee et al., 2002; Maatouk et al., 2006; Guibert et al., 2012; Hackett et al., 2012a).”
• Uncovering the role of 5-hydroxymethylcytosine in the epigenome (2011, background): “Nonetheless, DNA methylation patterns undergo genome-wide reprogramming during the establishment of primordial germ cells (PGCs) and after fertilizatio”
• Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by Aid deficiency (2010, neutral): “M ajo r ( 5) IA P (6) R2 (7 ) R1 (8 ) R4 (2 ) M et hy la tio n (% ) WT Aid–/– E13.”
• Epigenetic inheritance during the cell cycle (2009, background): “In a second wave, PGCs erase DNA methylation imprint”
• Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials (2019, background): “For example, DNA demethylation is important for primordial germ cells (PGCs) to gain pluripotent ability.(79,80) DNA demethylation is actively regulated by the TET protein family (teneleven translocation enzymes, TET1-3) via the removal of a methyl group from 5-mC.”
• Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse (2003, methodology): “Some demethylation of IAP elements and Line1 elements was also reported in primordial germ cells (Walsh et al., 1998; Hajkova et al., 2002).”