GSBS Student Publications

Title

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

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center

Date

7-1-2005

Document Type

Article

Medical Subject Headings

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, Genetic

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Mol Cell Biol. 2005 Jul;25(14):6140-53. Link to article on publisher's site

DOI of Published Version

10.1128/MCB.25.14.6140-6153.2005

Related Resources

Link to article in PubMed

Journal Title

Molecular and cellular biology

PubMed ID

15988025