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. 2017 Jan 15;31(2):101–126. doi: 10.1101/gad.291518.116

Figure 4.

Figure 4.

Varied roles of ADP-ribosylation in the regulation of gene regulation. (A) PAR turnover plays a critical role in hormone-dependent gene expression by generating ATP. Free PAR from PARG hydrolysis is further broken down by NUDIX5 to produce ATP. The ATP generated is used by ATP-dependent chromatin remodeling enzymes to modulate nucleosome occupancy at progesterone receptor (PR) target genes to stimulate transcription (Wright et al. 2016). (B) PARP-1 regulates the release of promoter-proximally paused RNA polymerase II into productive transcriptional elongation through ADP-ribosylation of the negative elongation factor (NELF) complex. Phosphorylation of NELF by the P-TEFb (positive-transcription elongation factor b) complex and subsequent ADP-ribosylation by PARP-1 results in the dissociation of NELF from RNA polymerase II, and the resulting release of pausing triggers productive elongation (Gibson et al. 2016). (C) ADP-ribosylation of C/EBPβ regulates the adipogenic transcriptional program. ADP-ribosylation by PARP-1 inhibits the binding of C/EBPβ to DNA. Upon exposure to adipogenic stimuli, there is loss of C/EBPβ PARylation and subsequent DNA binding. This turns on the expression of C/EBPβ-dependent proadipogenic genes (Luo et al. 2017).