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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Nuclear receptor coactivators: multiple enzymes, multiple complexes, multiple functions

N J McKenna1, J Xu, Z Nawaz

  • 1Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.

The Journal of Steroid Biochemistry and Molecular Biology
|July 27, 1999
PubMed

Insights

Nuclear receptors are crucial transcription factors influenced by hormones. They work with coactivator proteins, like SRC and p300/CBP, to regulate gene expression through chromatin modification.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Nuclear receptors are key regulators of gene expression, mediating hormonal effects.
  • They function as ligand-inducible transcription factors controlling cellular responses.

Purpose of the Study:

  • To elucidate the mechanisms by which nuclear receptors regulate gene transcription.
  • To identify and characterize the coregulator proteins involved in nuclear receptor signaling.

Main Methods:

  • Investigating the recruitment of coactivator proteins by liganded nuclear receptors.
  • Analyzing the enzymatic activities of coactivators, such as histone acetyltransferase (HAT) and chromatin remodeling.
  • Examining the structural organization of coactivator complexes.

Main Results:

  • Nuclear receptors recruit diverse coregulator proteins, including SRC family members, p300/CBP, BRG-1, E6-AP, and RPF-1.
  • Coactivators like p300/CBP and SRC possess histone acetyltransferase activity, impacting chromatin structure.
  • BRG-1, a SWI/SNF complex member, facilitates ATP-dependent chromatin remodeling.
  • Coactivators are organized into preformed subcomplexes, enabling efficient assembly.

Conclusions:

  • Nuclear receptors orchestrate gene expression by assembling intricate coactivator complexes.
  • These coactivators employ enzymatic activities (HAT, chromatin remodeling) and structural organization to modulate transcription.
  • The coordinated action of coactivators is essential for hormone-mediated gene regulation.

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