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

In mammalian primordial germ cells (PGCs), DNA demethylation is indispensible for parental imprint erasure, which is a reprogramming process essential for normal developmental potential. Thus, it is important to elucidate how DNA demethylation occurs in each imprinted region in PGCs and to determine...

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Veröffentlicht in:Scientific reports 2014-01, Vol.4 (1), p.3658, Article 3658
Hauptverfasser: Kawasaki, Yuki, Lee, Jiyoung, Matsuzawa, Ayumi, Kohda, Takashi, Kaneko-Ishino, Tomoko, Ishino, Fumitoshi
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container_start_page 3658
container_title Scientific reports
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creator Kawasaki, Yuki
Lee, Jiyoung
Matsuzawa, Ayumi
Kohda, Takashi
Kaneko-Ishino, Tomoko
Ishino, Fumitoshi
description In mammalian primordial germ cells (PGCs), DNA demethylation is indispensible for parental imprint erasure, which is a reprogramming process essential for normal developmental potential. Thus, it is important to elucidate how DNA demethylation occurs in each imprinted region in PGCs and to determine which DNA demethylation pathway, passive or active, essentially contributes to the erasure of the imprint. Here, we report that active DNA demethylation via a putative Poly(ADP-ribose) polymerase (PARP) pathway is involved in H19 -DMR imprint erasure in PGCs, as shown by an in vivo small molecule inhibitor assay. To the best of our knowledge, this is the first direct demonstration of a DNA replication-independent active DNA demethylation pathway in the erasure process of genomic imprinting in PGCs in vivo . The data also suggest that active DNA demethylation plays a significant role in the complete erasure of paternal imprinting in the female germ line.
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source Nature Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA/Free Journals; Free Full-Text Journals in Chemistry
subjects 13
13/31
45/22
631/136/2434
631/136/2435
631/61/212/177
631/80/641/151
Adenosine diphosphate
Animals
Cruelty to animals
Demethylation
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA Methylation - drug effects
Embryo, Mammalian
Female
Gene Expression Regulation, Developmental
Genomic Imprinting
Germ cells
Germ Cells - drug effects
Germ Cells - metabolism
Humanities and Social Sciences
Male
Mice
multidisciplinary
Poly(ADP-ribose)
Poly(ADP-ribose) polymerase
Poly(ADP-ribose) Polymerase Inhibitors
Poly(ADP-ribose) Polymerases - metabolism
Ribose
RNA, Long Noncoding - genetics
Science
title Active DNA demethylation is required for complete imprint erasure in primordial germ cells
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