Transcriptional Activation of Histone Genes Requires NPAT-Dependent Recruitment of TRRAP-Tip60 Complex to Histone Promoters during the G1/S Phase Transition

Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 02/2008; 28(1):435-47. DOI: 10.1128/MCB.00607-07
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ABSTRACT 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.

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Available from: Mary Pulvino, Aug 10, 2015
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    • "SLX2 might be involved in molecular events before the full establishment of SC based on its co-localization with γH2AX and its interaction with TIP60. While γH2AX is a marker for DSBs and their subsequent repairs (Celeste et al., 2002; Turner et al., 2004, 2005), TIP60 interacts with a variety of transcription factors and chromatin-remodeling complexes to facilitate DSBs repair (Ai et al., 2007; Auger et al., 2008; DeRan et al., 2008; Jha et al., 2008; Kusch et al., 2004; Yamagata and Kitabayashi, 2009). We tested whether SLX2 physically interacts with γH2AX, but could not detect an interaction (data not shown). "
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    • "We and others showed that the HATs CBP, p300 and Tip60 function in histone gene transcription [28,29]. Interestingly, these transcription factors are found to participate in DNA damage repair as well. "
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