The histone gene cell cycle regulator HiNF-P is a unique zinc finger transcription factor with a novel conserved auxiliary DNA-binding motif.

Accumulation of histone proteins is necessary for packaging of replicated DNA during the S phase of the cell cycle. Different mechanisms operate to regulate histone protein levels, and induction of human histone gene expression at the G1-S phase transition plays a critical role. The zinc finger HiNF-P and coactivator p220 (NPAT) proteins are key regulators of histone gene expression. Here, we describe a novel HiNF-P-specific conserved region (PSCR) located within the C-terminus that is present in HiNF-P homologues of all metazoan species that have been examined. The PSCR motif is required for activation of histone H4 gene transcription and contributes to DNA binding of HiNF-P. Thus, the PSCR module represents an auxiliary DNA-binding determinant that plays a critical role in mediating histone gene expression during the cell cycle and defines HiNF-P as a unique cell cycle regulatory member of the zinc finger transcription factor family.