Our previous data have shown that in L929 mouse fibroblasts the control of 
methylation pattern depends in part on poly(ADP-ribosyl)ation and that 
ADP-ribose polymers (PARs), both present on poly(ADP-ribosyl)ated PARP-1 and/or 
protein-free, have an inhibitory effect on Dnmt1 activity. Here we show that 
transient ectopic overexpression of CCCTC-binding factor (CTCF) induces PAR 
accumulation, PARP-1, and CTCF poly(ADP-ribosyl)ation in the same mouse 
fibroblasts. The persistence in time of a high PAR level affects the DNA 
methylation machinery; the DNA methyltransferase activity is inhibited with 
consequences for the methylation state of genome, which becomes diffusely 
hypomethylated affecting centromeric minor satellite and B1 DNA repeats. In 
vitro data show that CTCF is able to activate PARP-1 automodification even in 
the absence of nicked DNA. Our new finding that CTCF is able per se to activate 
PARP-1 automodification in vitro is of great interest as so far a burst of 
poly(ADP-ribosyl)ated PARP-1 has generally been found following introduction of 
DNA strand breaks. CTCF is unable to inhibit DNMT1 activity, whereas 
poly(ADP-ribosyl)ated PARP-1 plays this inhibitory role. These data suggest that 
CTCF is involved in the cross-talk between poly(ADP-ribosyl)ation and DNA 
methylation and underscore the importance of a rapid reversal of PARP activity, 
as DNA methylation pattern is responsible for an important epigenetic code.