Poly(ADP-ribose) polymerase 1 (PARP1, also known as ARTD1) is an abundant 
nuclear enzyme that plays important roles in DNA repair, gene transcription, and 
differentiation through the modulation of chromatin structure and function. In 
this work we identify a physical and functional poly(ADP-ribose)-mediated 
interaction of PARP1 with the E3 ubiquitin ligase UHRF1 (also known as NP95, 
ICBP90) that influences two UHRF1-regulated cellular processes. On the one hand, 
we uncovered a cooperative interplay between PARP1 and UHRF1 in the accumulation 
of the heterochromatin repressive mark H4K20me3. The absence of PARP1 led to 
reduced accumulation of H4K20me3 onto pericentric heterochromatin that coincided 
with abnormally enhanced transcription. The loss of H4K20me3 was rescued by the 
additional depletion of UHRF1. In contrast, although PARP1 also seemed to 
facilitate the association of UHRF1 with DNMT1, its absence did not impair the 
loading of DNMT1 onto heterochromatin or the methylation of pericentric regions, 
possibly owing to a compensating interaction of DNMT1 with PCNA. On the other 
hand, we showed that PARP1 controls the UHRF1-mediated ubiquitination of DNMT1 
to timely regulate its abundance during S and G2 phase. Together, this report 
identifies PARP1 as a novel modulator of two UHRF1-regulated 
heterochromatin-associated events: the accumulation of H4K20me3 and the 
clearance of DNMT1.