HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition.
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.
Mesh Terms:
Amino Acid Motifs, Animals, CDC2-CDC28 Kinases, Cell Cycle Proteins, Cell Nucleus, Chromatin, Cyclin E, Cyclin-Dependent Kinase 2, G1 Phase, Gene Expression Regulation, Histones, Humans, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Protein Interaction Mapping, Repressor Proteins, S Phase, Transcription, Genetic, Transcriptional Activation
Amino Acid Motifs, Animals, CDC2-CDC28 Kinases, Cell Cycle Proteins, Cell Nucleus, Chromatin, Cyclin E, Cyclin-Dependent Kinase 2, G1 Phase, Gene Expression Regulation, Histones, Humans, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Protein Interaction Mapping, Repressor Proteins, S Phase, Transcription, Genetic, Transcriptional Activation
Mol. Cell. Biol.
Date: Jul. 01, 2005
PubMed ID: 15988025
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