The poly ADP-ribosyl ation link

Enzymatically active PARP molecules have also been found involved in transcription in undamaged cells. Recent research on Drosophila has demonstrated that active puff loci are rich in PARPl and ADPR polymers, this being the necessary condition to induce chromatin decondensation and gene expression [159]. Mechanism of PARPl-mediated puffing and chromatin remodeling reinforces the idea previously suggested by Althaus to explain the role played by PARPl in DNA repair [160]. 

Therefore, there is no doubt that inhibition of PARP leads to DNA hypermethylation in vivo. But what is the molecular mechanism behind this phenomenon To get an insight into this mechanism, PARPs were inhibited at different phases of the cell cycle [41]. Both the mRNA and protein levels of Dnmtl were precociously increased in Gl/S phase. These elevated Dnmtl levels, affecting the normal equilibrium between p21 and Dnmtl in this phase, led to higher than normal levels of the PCNA-Dnmtl complex, and thus, to higher DNA methylation of the sequences replicated in early S phase (CpG islands are early replicating) (see Fig. 3d). 

Yet another hypothesis considers the somatic variant Hle of histone HI, in its poly(ADP-ribosyl)ated isoform, as a nuclear traw -acting factor involved in maintaining the methylation pattern on DNA [161]. 

the poly(ADP-ribosyl)ation process is involved in determining and/or maintaining the methylation patterns on DNA. Considering the importance for cells to preserve these patterns, further research will be performed to find additional proof to convalidate one or another mechanism or to identify other possibilities. 

DNA methylation and chromatin structure beyond the post-synthetic modifications of histones and other proteins 

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