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 ◽  
...  
2019 ◽  
Vol 31 (3) ◽  
pp. 509 ◽  
Author(s):  
Minli Yu ◽  
Dongfeng Li ◽  
Wanyan Cao ◽  
Xiaolu Chen ◽  
Wenxing Du

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.


2020 ◽  
Author(s):  
Sabine Dietmann ◽  
Michael J Keogh ◽  
Walfred Tang ◽  
Erna Magnusdottir ◽  
Toshihiro Kobayashi ◽  
...  

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.


2014 ◽  
Vol 56 (4) ◽  
pp. 564-579 ◽  
Author(s):  
Shinseog Kim ◽  
Ufuk Günesdogan ◽  
Jan J. Zylicz ◽  
Jamie A. Hackett ◽  
Delphine Cougot ◽  
...  

2020 ◽  
Author(s):  
Yu Tao ◽  
Xiinyu Xiang ◽  
Fei-Man Hsu ◽  
Julien Pontis ◽  
Didier Trono ◽  
...  

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.


PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e46036 ◽  
Author(s):  
Kentaro Mochizuki ◽  
Makoto Tachibana ◽  
Mitinori Saitou ◽  
Yuko Tokitake ◽  
Yasuhisa Matsui

Development ◽  
2013 ◽  
Vol 140 (14) ◽  
pp. 2892-2903 ◽  
Author(s):  
R. Ohno ◽  
M. Nakayama ◽  
C. Naruse ◽  
N. Okashita ◽  
O. Takano ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46927 ◽  
Author(s):  
Fabio Ciccarone ◽  
Francesca Gioia Klinger ◽  
Angela Catizone ◽  
Roberta Calabrese ◽  
Michele Zampieri ◽  
...  

2013 ◽  
Vol 12 (4) ◽  
pp. 470-478 ◽  
Author(s):  
John J. Vincent ◽  
Yun Huang ◽  
Pao-Yang Chen ◽  
Suhua Feng ◽  
Joseph H. Calvopiña ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruifeng Zhao ◽  
Qisheng Zuo ◽  
Xia Yuan ◽  
Kai Jin ◽  
Jing Jin ◽  
...  

AbstractThe allogeneic transplantation of primordial germ cells (PGCs) derived from somatic cells overcomes the limitation of avian cloning. Here, we transdifferentiate chicken embryo fibroblasts (CEFs) from black feathered Langshan chickens to PGCs and transplant them into White Plymouth Rock chicken embryos to produce viable offspring with characteristics inherited from the donor. We express Oct4/Sox2/Nanog/Lin28A (OSNL) to reprogram CEFs to induced pluripotent stem cells (iPSCs), which are further induced to differentiate into PGCs by BMP4/BMP8b/EGF. DNA demethylation, histone acetylation and glycolytic activation elevate the iPSC induction efficiency, while histone acetylation and glycolytic inhibition facilitate PGCs formation. The induced PGCs (iPGCs) are transplanted into the recipients, which are self-crossed to produce 189/509 somatic cells derived chicken with the donor’s characteristics. Microsatellite analysis and genome sequencing confirm the inheritance of genetic information from the donor. Thus, we demonstrate the feasibility of avian cloning from somatic cells.


Author(s):  
Amreek Singh ◽  
Warren G. Foster ◽  
Anna Dykeman ◽  
David C. Villeneuve

Hexachlorobenzene (HCB) is a known toxicant that is found in the environment as a by-product during manufacture of certain pesticides. This chlorinated chemical has been isolated from many tissues including ovary. When administered in high doses, HCB causes degeneration of primordial germ cells and ovary surface epithelium in sub-human primates. A purpose of this experiment was to determine a no-effect dose of the chemical on the rat ovary. The study is part of a comprehensive investigation on the effects of the compound on the biochemical, hematological, and morphological parameters in the monkey and rat.


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