Poly(ADP-ribosyl)ation acts in the DNA demethylation of mouse primordial germ cells also with DNA damage-independent roles.

Fabio Ciccarone (1) , Francesca Gioia Klinger (2) , Angela Catizone (3) , Roberta Calabrese (1, 4) , Michele Zampieri (1, 4) , Maria Giulia Bacalini (1, 4) , Massimo de Felici (2) , Paola Caiafa (1, 4)

1 Department of Cellular Biotechnologies and Haematology
2 Department of Public Health and Cell Biology
3 Department of Anatomy, Histology, Forensic Medicine and Orthopedics
4 Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti

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.

Domains: Cellular Biology; Molecular biology

Fabio Ciccarone, Francesca Gioia Klinger, Angela Catizone, Roberta Calabrese, Michele Zampieri, et al.. Poly(ADP-ribosyl)ation acts in the DNA demethylation of mouse primordial germ cells also with DNA damage-independent roles.. PLoS ONE, 2012, 7 (10), pp.e46927. ⟨10.1371/journal.pone.0046927⟩. ⟨pasteur-00955893⟩