HiNF-P is a bifunctional regulator of cell cycle controlled histone H4 gene transcription

Cell cycle progression beyond the G₁/S phase transition requires the activation of a transcription complex containing histone nuclear factor P (HiNF-P) and nuclear protein mapped to ataxia telangiectasia (p220 ^NPAT) in response to cyclin dependent kinase 2 (CDK2)/cyclin E signaling. We show here that the potent co-activating properties of HiNF-P/p220^NPAT on the histone H4 gene promoter, which are evident in the majority of human cell types, are sporadically neutralized in distinct somatic cell lines. In cells where HiNF-P and p220^NPAT do not activate the H4 gene promoter, HiNF-P instead represses transcription. Our data suggest that the cell type specific expression of the cyclin-dependent kinase inhibitory (CKI) protein p57^KIP2 inhibits the HiNF-P dependent activation of the histone H4 promoter. We propose that, analogous to E2F proteins and other cell cycle regulatory proteins, HiNF-P is a bifunctional transcriptional regulator that can activate or repress cell cycle controlled genes depending on the cellular context.