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 journalArticle

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Abstract

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
Volume25
Issue number14
DOIs
StatePublished - Jul 2005
Externally publishedYes

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Cyclin E
G1 Phase
S Phase
Histones
Cell Cycle
Phase Transition
Genes
Gene Expression
Eukaryotic Cells
DNA Replication
Transcriptional Activation
Molecular Biology
Genome

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition. / Miele, Angela; Braastad, Corey D.; Holmes, William F.; Mitra, Partha; Medina, Ricardo; Xie, Ronglin; Zaidi, Sayyed K.; Ye, Xin; Wei, Yue; Harper, J. Wade; van Wijnen, Andre J; Stein, Janet L.; Stein, Gary S.

In: Molecular and Cellular Biology, Vol. 25, No. 14, 07.2005, p. 6140-6153.

Research output: Contribution to journalArticle

Miele, A, Braastad, CD, Holmes, WF, Mitra, P, Medina, R, Xie, R, Zaidi, SK, Ye, X, Wei, Y, Harper, JW, van Wijnen, AJ, Stein, JL & Stein, GS 2005, 'HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition', Molecular and Cellular Biology, vol. 25, no. 14, pp. 6140-6153. https://doi.org/10.1128/MCB.25.14.6140-6153.2005
Miele, Angela ; Braastad, Corey D. ; Holmes, William F. ; Mitra, Partha ; Medina, Ricardo ; Xie, Ronglin ; Zaidi, Sayyed K. ; Ye, Xin ; Wei, Yue ; Harper, J. Wade ; van Wijnen, Andre J ; Stein, Janet L. ; Stein, Gary S. / HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 14. pp. 6140-6153.
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