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Related Experiment Videos

Tip60 is a co-repressor for STAT3.

Hui Xiao1, Jin Chung, Hung-Ying Kao

  • 1Department of Pharmacology and Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.

The Journal of Biological Chemistry
|January 29, 2003
PubMed
Summary

Tip60 (Tat-interactive protein, 60 kDa) protein represses gene expression by interacting with histone deacetylase 7 (HDAC7). This study shows Tip60 recruits HDAC7 to inhibit STAT3-mediated transcription, impacting cellular processes.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cellular Signaling

Background:

  • Tip60 (Tat-interactive protein, 60 kDa) possesses histone acetyltransferase activity and plays roles in DNA damage repair and apoptosis.
  • Tip60's function as a transcriptional co-activator or co-repressor is context-dependent.
  • STAT3 is a key transcription factor involved in various cellular processes, including proliferation and survival.

Purpose of the Study:

  • To investigate the mechanism by which Tip60 modulates transcription.
  • To determine if Tip60 interacts with and is regulated by histone deacetylase 7 (HDAC7).
  • To elucidate Tip60's role in STAT3-mediated gene expression.

Main Methods:

  • Reporter gene assays to assess transcriptional activity.
  • Co-immunoprecipitation to study protein-protein interactions between Tip60 and HDAC7.

Related Experiment Videos

  • Overexpression studies to evaluate the impact of Tip60 and HDAC7 on STAT3-driven gene expression.
  • Analysis of interleukin-9-induced c-myc expression.

    • Main Results:

    • Tip60 fused to the Gal4 DNA binding domain repressed reporter gene expression.
    • Tip60 physically associates with HDAC7 via its N-terminal zinc finger region.
    • HDAC7 activity was essential for Tip60-mediated repression.
    • Overexpression of Tip60 repressed STAT3-driven reporter gene expression, an effect enhanced by co-transfection with HDAC7.
    • Exogenous Tip60 expression abrogated interleukin-9-induced c-myc expression, which is dependent on STAT3.

    Conclusions:

    • Tip60 functions as a transcriptional repressor.
    • Tip60 directly interacts with HDAC7, and this interaction is crucial for Tip60's repressive function.
    • Tip60 represses STAT3-mediated trans-activation, in part, through the recruitment of HDAC7.
    • These findings reveal a novel mechanism of STAT3 regulation by Tip60 and HDAC7.