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. 2012 Feb 13;287(15):12405–12416. doi: 10.1074/jbc.M111.304469

FIGURE 6.

FIGURE 6.

Model for regulation of PARP-1 activity at target gene promoters by NMNAT-1. PARP-1 binds to target gene promoters where it blocks the binding of the linker histone H1 (21, 22) and PARylates chromatin-associated proteins, including transcription factors and histone-modifying enzymes, such as the histone H3 lysine 4 demethylase KDM5B (32) in an NAD+-dependent manner. PARP-1 interacts with and recruits NMNAT-1 to target gene promoters. NMNAT-1 supports PARP-1 activity in two ways: 1) by producing NAD+ for PARP-1 catalytic activity and 2) by stimulating PARP-1 catalytic activity in an NAD+ synthesis independent manner possibly through an allosteric mechanism. NMNAT-1 may also affect the gene regulatory activity of PARP-1 in a manner that is independent of the enzymatic activity of both PARP-1 and NMNAT-1. The functional interactions of PARP-1 and NMNAT-1 with chromatin may be modulated as end points of cellular signaling pathways (“Signals”) (20). P, PARP-1. H3K4me3, histone H3 lysine 4 trimethylation; NAM, nicotinamide; NAMPT, nicotinamide phosphoribosyltransferase.