The histone gene transcription factor HiNF-P stabilizes its cell cycle regulatory co-activator p220^NPAT

Orderly progression through the cell cycle requires the transcriptional activation of histone genes to support packaging of newly replicated DNA. Induction of human histone gene expression is mediated by a co-activation complex containing transcription factor HiNF-P and its cofactor p220 ^NPAT. Here, using cells synchronized in S-phase and in mitosis, as well as serum-stimulated cells, we have investigated how HiNF-P is regulated during the cell cycle and examined its stability relative to p220 ^NPAT. We find that while HiNF-P is maintained at steady-state levels throughout the cell cycle, both HiNF-P and p220^NPAT are actively degraded by the proteasome pathway. Importantly, elevation of HiNF-P levels enhances the stability of its co-activator p220^NPAT. The HiNF-P-dependent stabilization of p220^NPAT may reinforce signaling through the cyclin E/CDK2/p220^NPAT pathway and contribute to coordinate control of histone gene expression.