title: Active DNA demethylation is required for complete imprint erasure in primordial germ cells.
abstract: 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.
authors.affiliation: 1] Department of Epigenetics, Medical Research Institute, Japan [2] Global Center of Excellence Program for International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan [3].
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: 1] Department of Epigenetics, Medical Research Institute, Japan [2] Global Center of Excellence Program for International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan [3] Japan Science and Technology Agency, PRESTO, Japan [4].
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Epigenetics, Medical Research Institute, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Matsuzawa
authors.affiliation: Department of Epigenetics, Medical Research Institute, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohda
authors.affiliation: School of Health Sciences, Tokai University, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kaneko-Ishino
authors.affiliation: 1] Department of Epigenetics, Medical Research Institute, Japan [2] Global Center of Excellence Program for International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D005854:Germ Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics
chemical_list: C094335:H19 long non-coding RNA; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D062085:RNA, Long Noncoding; D011065:Poly(ADP-ribose) Polymerases