Transcriptional activation of the histone nuclear factor P (HiNF-P) gene by HiNF-P and its cyclin E/CDK2 responsive co-factor p220NPAT defines a novel autoregulatory loop at the G1/S phase transition

Gene. 2007 Nov 1;402(1-2):94-102. doi: 10.1016/j.gene.2007.07.027. Epub 2007 Aug 9.


Histone nuclear factor P (HiNF-P) activates histone H4 gene transcription at the G1/S phase transition upon association with its cyclin E/CDK2 responsive co-factor p220NPAT. Here we characterize the gene regulatory pathways that control the proliferation-related expression of HiNF-P. The HiNF-P locus contains a single TATA-less 0.6 kbp promoter with multiple phylogenetically conserved transcription factor recognition motifs. Transient reporter gene assays with HiNF-P promoter deletions show that there are at least three distinct activating regions (-387/-201, -201/-100 and -100/-1) that support maximal transcription. HiNF-P gene transcription is activated by SP1 through the -100/-1 domain and repressed by E2F1 through the -201/-100 domain. The multifunctional co-regulators CBP and p300 also stimulate HiNF-P gene transcription through the -201/-1 core promoter. Importantly, the HiNF-P promoter is activated by both HiNF-P and p220NPAT. This autoregulatory activation is further enhanced by cyclin E and CDK2, while blocked by CDK inhibition (i.e., p57KIP2 p27KIP1, p21CIP). Thus, the HiNF-P gene is a key non-histone target of p220NPAT and HiNF-P. The dependence of HiNF-P gene transcription on cyclin E/CDK2/p220NPAT signaling defines a novel feed-forward loop that may sustain HiNF-P expression in proliferating cells to support the cell cycle regulated synthesis of histone H4 proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cyclin E / metabolism*
  • Cyclin-Dependent Kinase 2 / metabolism*
  • G1 Phase*
  • HeLa Cells
  • Homeostasis / genetics
  • Humans
  • Mice
  • Models, Biological
  • Models, Genetic
  • NIH 3T3 Cells
  • Promoter Regions, Genetic
  • Regulatory Elements, Transcriptional
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • S Phase*
  • Signal Transduction / genetics
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcriptional Activation*


  • Cyclin E
  • HiNF-P protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • Cyclin-Dependent Kinase 2