HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition

Angela Miele, Corey D. Braastad, William F. Holmes, Partha Mitra, Ricardo Medina, Ronglin Xie, Sayyed K. Zaidi, Xin Ye, Yue Wei, J. Wade Harper, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Genome replication in eukaryotic cells necessitates the stringent coupling of histone biosynthesis with the onset of DNA replication at the G1/S phase transition. A fundamental question is the mechanism that links the restriction (R) point late in G1 with histone gene expression at the onset of S phase. Here we demonstrate that HiNF-P, a transcriptional regulator of replication-dependent histone H4 genes, interacts directly with p220 NPAT, a substrate of cyclin E/CDK2, to coactivate histone genes during S phase. HiNF-P and p220 are targeted to, and colocalize at, subnuclear foci (Cajal bodies) in a cell cycle-dependent manner. Genetic or biochemical disruption of the HiNF-P/p220 interaction compromises histone H4 gene activation at the G1/S phase transition and impedes cell cycle progression. Our results show that HiNF-P and p220 form a critical regulatory module that directly links histone H4 gene expression at the G1/S phase transition to the cyclin E/CDK2 signaling pathway at the R point.

Original languageEnglish (US)
Pages (from-to)6140-6153
Number of pages14
JournalMolecular and cellular biology
Issue number14
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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