PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin

The Pax gene family encodes transcription factors essential for organ and t issue development in higher eukaryotes. Pax proteins am modular with an N-t erminal DNA binding domain, a C-terminal transcription activation domain, a nd a transcription repression domain called the octapeptide. How these doma ins interact with the cellular machinery remains unclear. In this report, w e describe the isolation and characterization of a novel gene and its encod ed protein, PTIP, which binds to the activation domain of Pax2 and other Pa x proteins. PTIP binds to Pax2 in vitro, in the yeast two-hybrid assay and in tissue culture cells. The binding of PTIP to Pax2 is inhibited by the oc tapeptide repression domain. The PTIP protein contains five BRCT domains, f irst identified in BRCA1 and other nuclear proteins involved in DNA repair/ recombination or cell cycle control. Pax2 and PTIP co-localize in the cell nucleus to actively expressed chromatin and the nuclear matrix fraction. Fo r the first time, these results point to a link between Pax transcription f actors and active chromatin.