Figure 10.

Functional interplay between PARP-1, the nucleolar remodeling complex, and ncRNA in epigenetically silenced rRNA genes. (A) Active rRNA genes exhibit an open chromatin structure and are characterized by DNA hypomethylation as well as acetylation of histone H4. This open chromatin structure leads to binding of the transcription factors upstream binding factor (UBF), selectivity factor (SL1), and transcription initiation factor IA (TIF-IA) to the nucleosomal rDNA promoter. (B) To establish the silent state, NoRC is recruited to the rRNA gene promoter by interaction with the transcription termination factor (TTF-I). In subsequent steps, NoRC recruits the histone deacetylase HDAC1, DNA methyltransferase (DNMT), and noncoding pRNA. PARP-1 also interacts with NoRC via the noncoding pRNA and binds to the promoters of silent rRNA genes, promoting the formation of silent rDNA chromatin through PARylation of TIP5, histone, and PARP-1 itself.^90,220