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Related Experiment Videos

Nuclear receptor function requires a TFTC-type histone acetyl transferase complex.

Junn Yanagisawa1, Hirochika Kitagawa, Mitsuaki Yanagida

  • 1Institute of Molecular and Cellular Biosciences, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

Molecular Cell
|April 5, 2002
PubMed
Summary
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A novel coactivator complex, TRRP, containing GCN5 HAT, was identified and is essential for estrogen receptor alpha (ERalpha) function. This discovery reveals a third class of coactivator complex crucial for nuclear receptor activity.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Nuclear receptors (NRs) regulate gene transcription via ligand-dependent mechanisms.
  • Coactivator complexes, such as p160/CBP HAT and DRIP/TRAP/SMCC, are known to mediate NR function.
  • Understanding the diversity of coactivator complexes is crucial for deciphering transcriptional regulation.

Purpose of the Study:

  • To identify and characterize novel coactivator complexes involved in nuclear receptor transactivation.
  • To investigate the role of a newly identified human coactivator complex in estrogen receptor alpha (ERalpha) activity.
  • To determine the functional significance of this complex in cellular processes like proliferation.

Main Methods:

  • Identification and purification of a large human coactivator complex.

Related Experiment Videos

  • Biochemical assays to assess the interaction between the complex and liganded nuclear receptors.
  • In vitro transactivation assays using the purified complex.
  • Functional studies using antisense RNA to inhibit gene expression and cell growth.

    • Main Results:

    • A large human coactivator complex (TRRP) containing GCN5 HAT, TRRAP/PAF400, and TAF(II)30 was identified.
    • TRRP directly interacted with liganded ERalpha and other NRs, similar to known TFTC-type HAT complexes.
    • The purified TRRP complex enhanced ERalpha transactivation in vitro.
    • Inhibition of TRRAP expression using antisense RNA suppressed estrogen-dependent breast cancer cell growth.

    Conclusions:

    • The identified TRRP complex represents a third class of coactivator complex for nuclear receptor function.
    • This TFTC-type HAT complex plays a critical role in ERalpha-mediated transcription and estrogen-dependent cell proliferation.
    • The findings provide new insights into the molecular mechanisms of transcriptional regulation by nuclear receptors.