HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
Mol Cell Biol. 2005 Jul;25(14):6140-53. Link to article on publisher's site
Molecular and cellular biology
Miele, Angela; Braastad, Corey D.; Holmes, William F.; Mitra, Partha; Medina, Ricardo F.; Xie, Ronglin; Zaidi, Sayyed K.; Ye, Xin; Wei, Yue; Harper, J. Wade; Van Wijnen, Andre J.; Stein, Janet L.; and 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" (2005). GSBS Student Publications. 861.