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Transcriptional activation of histone genes requires NPAT-dependent recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S phase transition.

Transcriptional activation of histone subtypes is coordinately regulated and tightly coupled with the onset of DNA replication during S-phase entry. The underlying molecular mechanisms for such coordination and coupling are not well understood. The cyclin E-Cdk2 substrate NPAT has been shown to play an essential role in the transcriptional activation of histone genes at the G(1)/S-phase transition. Here, we show that NPAT interacts with components of the Tip60 histone acetyltransferase complex through a novel amino acid motif, which is functionally conserved in E2F and adenovirus E1A proteins. In addition, we demonstrate that transformation/transactivation domain-associated protein (TRRAP) and Tip60, two components of the Tip60 complex, associate with histone gene promoters at the G(1)/S-phase boundary in an NPAT-dependent manner. In correlation with the association of the TRRAP-Tip60 complex, histone H4 acetylation at histone gene promoters increases at the G(1)/S-phase transition, and this increase involves NPAT function. Suppression of TRRAP or Tip60 expression by RNA interference inhibits histone gene activation. Thus, our data support a model in which NPAT recruits the TRRAP-Tip60 complex to histone gene promoters to coordinate the transcriptional activation of multiple histone genes during the G(1)/S-phase transition.

Pubmed ID: 17967892

Authors

  • DeRan M
  • Pulvino M
  • Greene E
  • Su C
  • Zhao J

Journal

Molecular and cellular biology

Publication Data

January 19, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM65814

Mesh Terms

  • Acetylation
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cell Cycle Proteins
  • Cell Line
  • Conserved Sequence
  • G1 Phase
  • Histone Acetyltransferases
  • Histones
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Protein Binding
  • S Phase
  • Sequence Alignment
  • Transcription Factors
  • Transcriptional Activation