Abstract
Specification of primordial germ cells (PGCs) activates epigenetic reprogramming for totipotency, the elucidation of which remains a fundamental challenge. Here, we uncover regulatory principles for DNA methylation reprogramming during in vitro PGC specification, in which mouse embryonic stem cells (ESCs) are induced into epiblast-like cells (EpiLCs) and then PGC-like cells (PGCLCs). While ESCs reorganize their methylome to form EpiLCs, PGCLCs essentially dilute the EpiLC methylome at constant, yet different, rates between unique sequence regions and repeats. ESCs form hypomethylated domains around pluripotency regulators for their activation, whereas PGCLCs create demethylation-sensitive domains around developmental regulators by accumulating abundant H3K27me3 for their repression. Loss of PRDM14 globally upregulates methylation and diminishes the hypomethylated domains, but it preserves demethylation-sensitive domains. Notably, female ESCs form hypomethylated lamina-associated domains, while female PGCLCs effectively reverse such states into a more normal configuration. Our findings illuminate the unique orchestration of DNA methylation and histone modification reprogramming during PGC specification.
| Original language | English |
|---|---|
| Pages (from-to) | 87-103 |
| Number of pages | 17 |
| Journal | Developmental Cell |
| Volume | 39 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 10 2016 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Developmental Biology
- Cell Biology
Cite this
Global Landscape and Regulatory Principles of DNA Methylation Reprogramming for Germ Cell Specification by Mouse Pluripotent Stem Cells. / Shirane, Kenjiro; Kurimoto, Kazuki; Yabuta, Yukihiro; Yamaji, Masashi; Satoh, Junko; Ito, Shinji; Watanabe, Akira; Hayashi, Katsuhiko; Saitou, Mitinori; Sasaki, Hiroyuki.
In: Developmental Cell, Vol. 39, No. 1, 10.10.2016, p. 87-103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Global Landscape and Regulatory Principles of DNA Methylation Reprogramming for Germ Cell Specification by Mouse Pluripotent Stem Cells
AU - Shirane, Kenjiro
AU - Kurimoto, Kazuki
AU - Yabuta, Yukihiro
AU - Yamaji, Masashi
AU - Satoh, Junko
AU - Ito, Shinji
AU - Watanabe, Akira
AU - Hayashi, Katsuhiko
AU - Saitou, Mitinori
AU - Sasaki, Hiroyuki
PY - 2016/10/10
Y1 - 2016/10/10
N2 - Specification of primordial germ cells (PGCs) activates epigenetic reprogramming for totipotency, the elucidation of which remains a fundamental challenge. Here, we uncover regulatory principles for DNA methylation reprogramming during in vitro PGC specification, in which mouse embryonic stem cells (ESCs) are induced into epiblast-like cells (EpiLCs) and then PGC-like cells (PGCLCs). While ESCs reorganize their methylome to form EpiLCs, PGCLCs essentially dilute the EpiLC methylome at constant, yet different, rates between unique sequence regions and repeats. ESCs form hypomethylated domains around pluripotency regulators for their activation, whereas PGCLCs create demethylation-sensitive domains around developmental regulators by accumulating abundant H3K27me3 for their repression. Loss of PRDM14 globally upregulates methylation and diminishes the hypomethylated domains, but it preserves demethylation-sensitive domains. Notably, female ESCs form hypomethylated lamina-associated domains, while female PGCLCs effectively reverse such states into a more normal configuration. Our findings illuminate the unique orchestration of DNA methylation and histone modification reprogramming during PGC specification.
AB - Specification of primordial germ cells (PGCs) activates epigenetic reprogramming for totipotency, the elucidation of which remains a fundamental challenge. Here, we uncover regulatory principles for DNA methylation reprogramming during in vitro PGC specification, in which mouse embryonic stem cells (ESCs) are induced into epiblast-like cells (EpiLCs) and then PGC-like cells (PGCLCs). While ESCs reorganize their methylome to form EpiLCs, PGCLCs essentially dilute the EpiLC methylome at constant, yet different, rates between unique sequence regions and repeats. ESCs form hypomethylated domains around pluripotency regulators for their activation, whereas PGCLCs create demethylation-sensitive domains around developmental regulators by accumulating abundant H3K27me3 for their repression. Loss of PRDM14 globally upregulates methylation and diminishes the hypomethylated domains, but it preserves demethylation-sensitive domains. Notably, female ESCs form hypomethylated lamina-associated domains, while female PGCLCs effectively reverse such states into a more normal configuration. Our findings illuminate the unique orchestration of DNA methylation and histone modification reprogramming during PGC specification.
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UR - http://www.scopus.com/inward/citedby.url?scp=84992660402&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2016.08.008
DO - 10.1016/j.devcel.2016.08.008
M3 - Article
C2 - 27642137
AN - SCOPUS:84992660402
VL - 39
SP - 87
EP - 103
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 1
ER -