A NUCLEAR FACTOR OTHER THAN SP1 BINDS THE GC-RICH PROMOTER OF THE GENE ENCODING RAT POLY(ADP-RIBOSE) POLYMERASE IN-VITRO

Poly(ADP-ribose) polymerase is a nuclear enzyme that has been shown to exert a key role in many important cellular functions, including DNA repair. Its activity was shown to vary substantially between tissues, the testis and the thymus expressed the highest levels of PARP whereas the liver and the kidney (as well as a few other tissues) expressed o nly low levels of PARP proteins in vivo. The GC-rich nature of its ups tream gene promoter, along with the lack of TATA and CAAT boxes, a fea ture common to most housekeeping genes, is consistent with a major reg ulatory function played by the positive transcription factor Sp1 in ra t PARP gene transcription. Sp1 was indeed recently shown to interact w ith five distinct GC or GT boxes present in the rat PARP promoter. How ever, the observation that PARP activity was lower in rat liver than i n other tissues was shown not to be the result of reduced Sp1 activity in liver cells but rather suggests the interplay of nuclear proteins other than Sp1 that are required to restrict PARP expression in this o rgan and maybe in others (such as the kidney). In this study, we inves tigated this possibility further by defining whether other nuclear pro teins might bind the PARP promoter to modulate its transcription in li ver cells. As a result, we identified a nuclear factor distinct from S p1 that binds the PARP promoter at a site overlapping the F2 Sp1 eleme nt previously identified. Our results suggest that this protein likely belongs to the CTF-NF1 family of transcription factors.