NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription.
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.
Zhao
J
J
Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA. jiyong_zhao@urmc.rochester.edu
Kennedy
B K
BK
Lawrence
B D
BD
Barbie
D A
DA
Matera
A G
AG
Fletcher
J A
JA
Harlow
E
E
D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication; D005786:Gene Expression Regulation; D006657:Histones / Q000096:biosynthesis*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016196:S Phase
D018797:Cell Cycle Proteins; D002843:Chromatin; D019927:Cyclin E; D006657:Histones; C101693:NPAT protein, human; D009687:Nuclear Proteins; D011506:Proteins; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases