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4. Poly(ADP-ribosyl)ation Acts in the DNA Demethylation of Mouse Primordial Germ Cells Also with DNA Damage-Independent Roles

Author

Angela Catizone, Massimo De Felici, Paola Caiafa, Maria Giulia Bacalini, Francesca Gioia Klinger, Fabio Ciccarone, Michele Zampieri, Roberta Calabrese, Ciccarone, Fabio, Klinger, Francesca Gioia, Catizone, Angela, Calabrese, Roberta, Zampieri, Michele, Bacalini, Maria Giulia, de Felici, Massimo, Caiafa, Paola, Department of Cellular Biotechnologies and Haematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Department of Public Health and Cell Biology, Università degli Studi di Roma Tor Vergata [Roma], Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), and Grants from Ministero della Salute (PC), from International FIRB 2006 (RBIN06E9Z8_003) and from Ministero dell'Istruzione, dell'Universita e della Ricerca (PRIN 2008, PC, MDF), Italy.

Subjects
Male, Poly Adenosine Diphosphate Ribose, Time Factors, Mouse, Poly (ADP-Ribose) Polymerase-1, lcsh:Medicine, Mice, MESH: DNA Methylation, 0302 clinical medicine, PARP1, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Gene Expression Regulation, Developmental, Molecular Cell Biology, MESH: Animals, DNA (Cytosine-5-)-Methyltransferases, lcsh:Science, Poly(ADP-ribose) Polymerase, Proto-Oncogene Protein, 0303 health sciences, Settore BIO/17, Multidisciplinary, Chromosome Biology, Reverse Transcriptase Polymerase Chain Reaction, Medicine (all), parp1, epigenetics, dnmt1, tet1, 5-hydroxymethylcytosine, Gene Expression Regulation, Developmental, Genomics, Animal Models, Chromatin, MESH: DNA (Cytosine-5-)-Methyltransferase, DNA-Binding Proteins, MESH: Poly Adenosine Diphosphate Ribose, DNA methylation, Female, Cellular Types, Poly(ADP-ribose) Polymerases, DNA modification, Reprogramming, Research Article, DNA (Cytosine-5-)-Methyltransferase 1, Time Factor, DNA damage, DNA-Binding Protein, Poly ADP ribose polymerase, Blotting, Western, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Germ Cell, 03 medical and health sciences, Model Organisms, MESH: Analysis of Variance, Proto-Oncogene Proteins, Genetics, MESH: Blotting, Western, Animals, Epigenetics, MESH: Mice, 030304 developmental biology, MESH: DNA Damage, Analysis of Variance, Biochemistry, Genetics and Molecular Biology (all), Animal, MESH: Poly(ADP-ribose) Polymerases, MESH: Time Factors, lcsh:R, MESH: Embryo, Mammalian, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA Methylation, Embryo, Mammalian, Molecular biology, MESH: Male, MESH: Proto-Oncogene Proteins, MESH: Germ Cells, Germ Cells, DNA demethylation, Agricultural and Biological Sciences (all), DNA (Cytosine-5-)-Methyltransferase, lcsh:Q, Gene expression, MESH: Female, MESH: DNA-Binding Proteins, 030217 neurology & neurosurgery, Developmental Biology, DNA Damage
Abstract

Poly(ADP-ribosyl)ation regulates chromatin structure and transcription driving epigenetic events. In particular, Parp1 is able to directly influence DNA methylation patterns controlling transcription and activity of Dnmt1. Here, we show that ADP-ribose polymer levels and Parp1 expression are noticeably high in mouse primordial germ cells (PGCs) when the bulk of DNA demethylation occurs during germline epigenetic reprogramming in the embryo. Notably, Parp1 activity is stimulated in PGCs even before its participation in the DNA damage response associated with active DNA demethylation. We demonstrate that PARP inhibition impairs both genome-wide and locus-specific DNA methylation erasure in PGCs. Moreover, we evidence that impairment of PARP activity causes a significant reduction of expression of the gene coding for Tet1 hydroxylases involved in active DNA demethylation. Taken together these results demonstrate new and adjuvant roles of poly(ADP-ribosyl)ation during germline DNA demethylation and suggest its possible more general involvement in genome reprogramming. © 2012 Ciccarone et al.

Published
2012

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