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PMID: 10995386 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription.

Genes & development ·Vol. 14 ·No. 18 ·2000-09-15 ·Pages 2283-97

Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E

Abstract

In eukaryotic cells, histone gene expression is one of the major events that mark entry into S phase. While this process is tightly linked to cell cycle position, how it is regulated by the cell cycle machinery is not known. Here we show that NPAT, a substrate of the cyclin E-Cdk2 complex, is associated with human replication-dependent histone gene clusters on both chromosomes 1 and 6 in S phase. We demonstrate that NPAT activates histone gene transcription and that this activation is dependent on the promoter elements (SSCSs) previously proposed to mediate cell cycle-dependent transcription. Cyclin E is also associated with the histone gene loci, and cyclin E-Cdk2 stimulates the NPAT-mediated activation of histone gene transcription. Thus, our results both show that NPAT is involved in a key S phase event and provide a link between the cell cycle machinery and activation of histone gene transcription.

MeSH Terms
CDC2-CDC28 Kinases Cell Cycle Proteins Cell Line Cell Nucleus/metabolism Chromatin/metabolism Cyclin E/genetics,metabolism Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases/genetics,metabolism DNA Replication Gene Expression Regulation Histones/biosynthesis Humans In Situ Hybridization, Fluorescence Microscopy, Fluorescence Nuclear Proteins Protein Serine-Threonine Kinases/genetics,metabolism Proteins/genetics,metabolism S Phase
Chemicals
Cell Cycle Proteins Chromatin Cyclin E Histones NPAT protein, human Nuclear Proteins Proteins Protein Serine-Threonine Kinases CDC2-CDC28 Kinases CDK2 protein, human Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zhao J
Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA. jiyong_zhao@urmc.rochester.edu
Kennedy B K
Lawrence B D
Barbie D A
Matera A G
Fletcher J A
Harlow E
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Email
jiyong_zhao@urmc.rochester.edu
Published
2000-09-15
Pages
2283-97
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316937
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053034 · United States
External Links
PubMed source PMC Full Text View journal details
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