ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites

Poly(ADP-ribosyl)ation (PARylation) is involved in the maintaining of genomic methylation pattern through its control of DNA methyltranferase 1 (Dnmt1) activity. Our previous findings indicated the CCCTC binding factor/Ctcf as an important player in the mechanism by which PARylation controls the non methylated status of some CpG rich regions. Ctcf is able to activate Poly (ADP-ribose) polymerase 1 (Parp1) which, in turn, inhibits Dnmt1 activity by ADP-ribose polymers located on Parp1 itself. According to this mechanism, Ctcf may act in preserving the epigenetic pattern at promoters of important housekeeping genes. Data here reported evidence 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 maintaining of the non methylated status of some Ctcf-bound CpGs. All this suggests a mechanism by which Parp1, tethered and activated at specific DNA targets by Ctcf, preserves their methylation free status.