title: Poly(ADP-ribosylation) regulates chromatin organization through histone H3 modification and DNA methylation of the first cell cycle of mouse embryos.
abstract: We examined the roles of poly(ADP-ribosylation) in chromatin remodeling during the first cell cycle of mouse embryos. Drug-based inhibition of poly(ADP-ribosylation) by a PARP inhibitor, PJ-34, revealed up-regulation of dimethylation of histone H3 at lysine 4 in male pronuclei and down-regulation of dimethylation of histone H3 at lysine 9 (H3K9) and lysine 27 (H3K27). Association of poly(ADP-ribosylation) with histone modification was suggested to be supported by the interaction of Suz12, a histone methyltransferase in the polycomb complex, with Parp1. PARP activity was suggested to be required for a proper localization and maintenance of Suz12 on chromosomes. Notably, DNA methylation level of female pronuclei in one-cell embryos was robustly decreased by PJ-34. Electron microscopic analysis showed a frequent appearance of unusual electron-dense areas within the female pronuclei, implying the disorganized and hypercondensed chromatin ultrastructure. These results show that poly(ADP-ribosylation) is important for the integrity of non-equivalent epigenetic dynamics of pronuclei during the first cell cycle of mouse embryos.
authors.affiliation: Advanced Medical Science Research Department, Mitsubishi Chemical Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaragi 314-0255, Japan. osada.tomoharu@mg.medience.co.jp
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Osada
authors.forename: Anna-Margareta
authors.initials: AM
authors.lastname: Rydén
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Masutani
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002843:Chromatin / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D006657:Histones / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010616:Phenanthrenes / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases