HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition
Authors
Miele, AngelaBraastad, 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.
Stein, Gary S.
UMass Chan Affiliations
Department of Cell Biology and Cancer CenterGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2005-07-01Keywords
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 (Genetics); Protein Interaction Mapping; Repressor Proteins; S Phase; Transcription, GeneticLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Mol Cell Biol. 2005 Jul;25(14):6140-53. Link to article on publisher's siteDOI
10.1128/MCB.25.14.6140-6153.2005Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34205PubMed ID
15988025Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/MCB.25.14.6140-6153.2005