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Stem Cell Reports. 2016 Dec 13;7(6):1072-1086. doi: 10.1016/j.stemcr.2016.10.007. Epub 2016 Nov 17.

PRDM14 Drives OCT3/4 Recruitment via Active Demethylation in the Transition from Primed to Naive Pluripotency.

Author information

1
Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan; Department of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan.
2
Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan.
3
Phyloinformatics Unit, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima-minami, Kobe 650-0047, Japan.
4
Department of Stem Cell Biology and Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
5
Department of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan.
6
Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan. Electronic address: yseki@kwansei.ac.jp.

Abstract

Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here, we exploited the in vitro differentiation of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the molecular and epigenetic functions of PR domain-containing 14 (PRDM14). We found that Prdm14 overexpression in EpiLCs induced their conversion to ESC-like cells even in the absence of leukemia inhibitory factor in adherent culture. This was impaired by the loss of Kruppel-like factor 2 and ten-eleven translocation (TET) proteins. Furthermore, PRDM14 recruited OCT3/4 to the enhancer regions of naive pluripotency genes via TET-base excision repair-mediated demethylation. Our results provide evidence that PRDM14 establishes a transcriptional network for naive pluripotency via active DNA demethylation.

KEYWORDS:

DNA methylation; embryonic stem cells; epiblast; epigenetics; pluripotency; primordial germ cells; reprogramming

PMID:
27866876
PMCID:
PMC5161533
DOI:
10.1016/j.stemcr.2016.10.007
[Indexed for MEDLINE]
Free PMC Article

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