The expanding role ofPARPs in the establishment and maintenance of heterochromatin

Abstract

Poly(ADP-ribose) polymerases (PARPs) are enzymes that transfer poly(ADP-ribose) (PAR) groups to target proteins, and thereby affect various nuclear and cytoplasmic processes. The activity of PARP family members, such as PARP1 and PARP2, is tied to cellular signalling pathways, and, through poly(ADP-ribosyl)ation, they ultimately promote changes in chromatin architecture, gene expression, and the location and activity of proteins that mediate signalling responses. A growing body of evidence suggest that PARPs, particularly PARP1 and PARP2, also operate at heterochromatic regions such as the inactive X chromosome, telomeres, pericentric heterochromatin and silent ribosomal RNA (rRNA) genes. Both proteins localize to heterochromatic sites and often associate with or poly(ADP-ribosyl)ate histones and heterochromatin-binding proteins, thereby modulating their activities. In this review, we describe current knowledge concerning the role of PARPs in establishment and inheritance of heterochromatic structures, and highlight how their contribution affects biological outcomes.