scholarly journals PRMT5 Protects Genomic Integrity during Global DNA Demethylation in Primordial Germ Cells and Preimplantation Embryos

2014 ◽  
Vol 56 (4) ◽  
pp. 564-579 ◽  
Author(s):  
Shinseog Kim ◽  
Ufuk Günesdogan ◽  
Jan J. Zylicz ◽  
Jamie A. Hackett ◽  
Delphine Cougot ◽  
...  
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Dna Demethylation ◽  
Preimplantation Embryos ◽  
Genomic Integrity

scholarly journals Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage

2020 ◽  
Author(s):  
Qifan Zhu ◽  
Fei Sang ◽  
Sarah Withey ◽  
Walfred Tang ◽  
Sabine Dietmann ◽  
...  
Keyword(s):  
Large Scale ◽  
Excision Repair ◽  
Primordial Germ Cells ◽  
Epigenetic Inheritance ◽  
Dna Demethylation ◽  
Epigenetic Reprogramming ◽  
Preimplantation Embryos ◽  
Gene Coding ◽  
Base Excision

SummaryInvestigations on the human germline and programming are challenging due to limited access to embryonic material. However, the pig as a model may provide insight on transcriptional network and epigenetic reprogramming applicable to both species. Here we show that during the pre- and early migratory stages pig primordial germ cells (PGCs) initiate large-scale epigenetic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and potentially base excision repair (BER). There is also macroH2A1 depletion and increased H3K27me3, as well as X chromosome reactivation (XCR) in females. Concomitantly, there is dampening of glycolytic metabolism genes and re-expression of some pluripotency genes like those in preimplantation embryos. We identified evolutionarily young transposable elements and gene coding regions resistant to DNA demethylation in acutely hypomethylated gonadal PGCs, with potential for transgenerational epigenetic inheritance. Detailed insights into the pig germline will likely contribute significantly to advances in human germline biology, including in vitro gametogenesis.

Effects of ten–eleven translocation 1 (Tet1) on DNA methylation and gene expression in chicken primordial germ cells

2019 ◽  
Vol 31 (3) ◽  
pp. 509 ◽  
Author(s):  
Minli Yu ◽  
Dongfeng Li ◽  
Wanyan Cao ◽  
Xiaolu Chen ◽  
Wenxing Du
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Germ Cells ◽  
Dna Methyltransferase ◽  
Primordial Germ Cells ◽  
Dna Demethylation ◽  
Caveolin 1 ◽  
Expression Of Genes ◽  
Deleted In Azoospermia

Ten–eleven translocation 1 (Tet1) is involved in DNA demethylation in primordial germ cells (PGCs); however, the precise regulatory mechanism remains unclear. In the present study the dynamics of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in developing PGCs and the role of Tet1 in PGC demethylation were analysed. Results show that 5mC levels dropped significantly after embryonic Day 4 (E4) and 5hmC levels increased reaching a peak at E5–E5.5. Interestingly, TET1 protein was highly expressed during E5 to E5.5, which showed a consistent trend with 5hmC. The expression of pluripotency-associated genes (Nanog, PouV and SRY-box 2 (Sox2)) and germ cell-specific genes (caveolin 1 (Cav1), piwi-like RNA-mediated gene silencing 1 (Piwi1) and deleted in azoospermia-like (Dazl)) was upregulated after E5, whereas the expression of genes from the DNA methyltransferase family was decreased. Moreover, the Dazl gene was highly methylated in early PGCs and then gradually hypomethylated. Knockdown of Tet1 showed impaired survival and proliferation of PGCs, as well as increased 5mC levels and reduced 5hmC levels. Further analysis showed that knockdown of Tet1 led to elevated DNA methylation levels of Dazl and downregulated gene expression including Dazl. Thus, this study reveals the dynamic epigenetic reprogramming of chicken PGCs invivo and the molecular mechanism of Tet1 in regulating genomic DNA demethylation and hypomethylation of Dazl during PGC development.

scholarly journals Transposable elements resistant to epigenetic resetting in the human germline are epigenetic hotspots for development and disease

2020 ◽  
Author(s):  
Sabine Dietmann ◽  
Michael J Keogh ◽  
Walfred Tang ◽  
Erna Magnusdottir ◽  
Toshihiro Kobayashi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cerebral Cortex ◽  
Transposable Elements ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Dna Demethylation ◽  
Hair Color ◽  
Epigenetic Changes ◽  
Early Human ◽  
Development And Evolution

ABSTRACTDespite the extensive erasure of DNA methylation in the early human germline, nearly eight percent of CpGs are resistant to the epigenetic resetting in the acutely hypomethylated primordial germ cells (week 7-9 hPGCs). Whether this occurs stochastically or represents relatively conserved layer of epigenetic information is unclear. Here we show that several predominantly hominoid-specific families of transposable elements (TEs) consistently resist DNA demethylation (henceforth called hPGC-methylated TEs or ‘escapees’) during the epigenetic resetting of hPGCs. Some of them undergo subsequent dynamic epigenetic changes during embryonic development. Our analysis of the fetal cerebral cortex also revealed multiple classes of young hPGC-methylated TEs within putative and established enhancers. Remarkably, specific hPGC-methylated TE subfamilies were associated with a multitude of adaptive human traits, including hair color and intelligence, and diseases including schizophrenia and Alzheimer’s disease. We postulate that hPGC-methylated TEs represent potentially heritable information within the germline with a role in human development and evolution.

scholarly journals Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominin-Specific Viral Infections

2020 ◽  
Author(s):  
Yu Tao ◽  
Xiinyu Xiang ◽  
Fei-Man Hsu ◽  
Julien Pontis ◽  
Didier Trono ◽  
...  
Keyword(s):  
Germ Cells ◽  
Viral Infections ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Dna Demethylation ◽  
Human Reproduction ◽  
Epigenetic Landscape

Abstract Germ cells are essential to pass DNA from one generation to the next. In human reproduction, germ cell development begins with the specification of primordial germ cells (PGCs) and a failure to specify PGCs leads to human infertility. Recent studies have revealed that the transcription factor network required for PGC specification has diverged in mammals, and this has a significant impact on our understanding of human reproduction. Here, we evaluated the emerging epigenetic landscape during hPGC specification using a combination of in vivo and in vitro analysis of hPGCs/hPGC-like cells (hPGCLCs) and human embryonic stem cells (hESCs). Our data reveals that hominid restricted Transposable Elements (TEs) partly derived from ancient viruses are pre-bound by the transcription factors TFAP2C and NANOG in undifferentiated hESCs, become transcriptionally induced during PGC specification and undergo dynamic epigenetic reprogramming leading to increased chromatin accessibility, localized DNA demethylation and establishment of broad peaks of H3K27ac. Using KRAB mediated CRISPRi we show that blocking this remodeling has a significant impact on hPGC specification. In summary, our data reveals that human reproduction requires the establishment of an epigenetic landscape during hPGC specification driven by the acquisition of hominid-specific TEs that were derived from ancient viral infections that entered the hominid germline less than 5 million years ago.

scholarly journals The Role of Mutant p63 in Female Fertility

2021 ◽  
Vol 22 (16) ◽  
pp. 8968
Author(s):  
Yi Luan ◽  
Pauline Xu ◽  
Seok-Yeong Yu ◽  
So-Youn Kim
Keyword(s):  
Germ Cells ◽  
Essential Role ◽  
Primordial Germ Cells ◽  
Genomic Integrity ◽  
Biological Functions ◽  
Ovarian Insufficiency ◽  
P53 Family ◽  
C Terminus ◽  
N Terminus

The transcription factor p63, one of the p53 family members, plays an essential role in regulating maternal reproduction and genomic integrity as well as epidermal development. TP63 (human)/Trp63 (mouse) produces multiple isoforms: TAp63 and ΔNp63, which possess a different N-terminus depending on two different promoters, and p63a, p63b, p63g, p63δ, and p63ε as products of alternative splicing at the C-terminus. TAp63 expression turns on in the nuclei of primordial germ cells in females and is maintained mainly in the oocyte nuclei of immature follicles. It has been established that TAp63 is the genomic guardian in oocytes of the female ovaries and plays a central role in determining the oocyte fate upon oocyte damage. Lately, there is increasing evidence that TP63 mutations are connected with female infertility, including isolated premature ovarian insufficiency (POI) and syndromic POI. Here, we review the biological functions of p63 in females and discuss the consequences of p63 mutations, which result in infertility in human patients.

scholarly journals Implication of DNA Demethylation and Bivalent Histone Modification for Selective Gene Regulation in Mouse Primordial Germ Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e46036 ◽  
Author(s):  
Kentaro Mochizuki ◽  
Makoto Tachibana ◽  
Mitinori Saitou ◽  
Yuko Tokitake ◽  
Yasuhisa Matsui
Keyword(s):  
Gene Regulation ◽  
Histone Modification ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Dna Demethylation

scholarly journals Active DNA demethylation is required for complete imprint erasure in primordial germ cells

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuki Kawasaki ◽  
Jiyoung Lee ◽  
Ayumi Matsuzawa ◽  
Takashi Kohda ◽  
Tomoko Kaneko-Ishino ◽  
...  
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Dna Demethylation ◽  
Active Dna Demethylation

scholarly journals A replication-dependent passive mechanism modulates DNA demethylation in mouse primordial germ cells

Development ◽  
2013 ◽  
Vol 140 (14) ◽  
pp. 2892-2903 ◽  
Author(s):  
R. Ohno ◽  
M. Nakayama ◽  
C. Naruse ◽  
N. Okashita ◽  
O. Takano ◽  
...  
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Dna Demethylation ◽  
Passive Mechanism

scholarly journals Poly(ADP-ribosyl)ation Acts in the DNA Demethylation of Mouse Primordial Germ Cells Also with DNA Damage-Independent Roles

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46927 ◽  
Author(s):  
Fabio Ciccarone ◽  
Francesca Gioia Klinger ◽  
Angela Catizone ◽  
Roberta Calabrese ◽  
Michele Zampieri ◽  
...  
Keyword(s):  
Dna Damage ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Dna Demethylation
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