title: ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites.
abstract: PARylation [poly(ADP-ribosyl)ation] is involved in the maintenance of genomic methylation patterns through its control of Dnmt1 [DNA (cytosine-5)-methyltransferase 1] activity. Our previous findings indicated that Ctcf (CCCTC-binding factor) may be an important player in key events whereby PARylation controls the unmethylated status of some CpG-rich regions. Ctcf is able to activate Parp1 [poly(ADP-ribose) polymerase 1], which ADP-ribosylates itself and, in turn, inhibits DNA methylation via non-covalent interaction between its ADP-ribose polymers and Dnmt1. By such a mechanism, Ctcf may preserve the epigenetic pattern at promoters of important housekeeping genes. The results of the present study showed Dnmt1 as a new protein partner of Ctcf. Moreover, we show that Ctcf forms a complex with Dnmt1 and PARylated Parp1 at specific Ctcf target sequences and that PARylation is responsible for the maintenance of the unmethylated status of some Ctcf-bound CpGs. We suggest a mechanism by which Parp1, tethered and activated at specific DNA target sites by Ctcf, preserves their methylation-free status.
authors: Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, Italy.
authors: Michele
authors: M
authors: Zampieri
authors: Tiziana
authors: T
authors: Guastafierro
authors: Roberta
authors: R
authors: Calabrese
authors: Fabio
authors: F
authors: Ciccarone
authors: Maria G
authors: MG
authors: Bacalini
authors: Anna
authors: A
authors: Reale
authors: Mariagrazia
authors: M
authors: Perilli
authors: Claudio
authors: C
authors: Passananti
authors: Paola
authors: P
authors: Caiafa
mesh_terms: D000076246:CCCTC-Binding Factor; D018899:CpG Islands / Q000502:physiology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D046912:Multiprotein Complexes / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D000076246:CCCTC-Binding Factor; D046912:Multiprotein Complexes; D012097:Repressor Proteins; D011064:Poly Adenosine Diphosphate Ribose; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D011065:Poly(ADP-ribose) Polymerases