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

Genes Dev. 2000 Sep 15;14(18):2283-97.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CDC2-CDC28 Kinases*
  • Cell Cycle Proteins*
  • Cell Line
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • Cyclin E / genetics*
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • DNA Replication*
  • Gene Expression Regulation
  • Histones / biosynthesis*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Microscopy, Fluorescence
  • Nuclear Proteins*
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteins / genetics*
  • Proteins / metabolism
  • S Phase


  • 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