Journal
GENES & DEVELOPMENT
Volume 14, Issue 18, Pages 2283-2297Publisher
COLD SPRING HARBOR LAB PRESS
DOI: 10.1101/gad.827700
Keywords
NPAT; cyclin E-Cdk2; histone gene transcription; nuclear foci
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Funding
- NIGMS NIH HHS [R01 GM053034] Funding Source: Medline
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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.
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