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The human SPT20-containing SAGA complex plays a direct role in the regulation of endoplasmic reticulum stress-induced

Zita Nagy1, Anne Riss, Christophe Romier

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS, ULP, INSERM U.964, Parc d'Innovation, Illkirch Cedex, CU de Strasbourg, France.

Molecular and Cellular Biology
|December 31, 2008
PubMed

Insights

The human SPT20 protein is crucial for the integrity of the human SAGA (hSAGA) complex, which specifically regulates genes involved in endoplasmic reticulum stress response.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Chromatin Remodeling

Background:

  • Eukaryotic transcription activators signal gene expression changes within chromatin.
  • The SAGA coactivator complex remodels chromatin and possesses histone acetyltransferase and deubiquitination activities.
  • The specific role of SAGA in regulating transcription at distinct genomic loci remains unclear.

Purpose of the Study:

  • To identify and characterize the human homologue of yeast Spt20.
  • To determine the role of human SPT20 (hSPT20) in the human SAGA (hSAGA) complex.
  • To investigate the function of hSAGA in transcriptional regulation, particularly in response to stress.

Main Methods:

  • Mass spectrometry to identify protein interactions.
  • Immunoprecipitation and Western blot analysis to confirm protein presence and interactions.
  • Gene knockdown experiments to assess functional requirements.

Main Results:

  • Human SPT20 (hSPT20) was identified as a subunit of the human SAGA (hSAGA) complex and is essential for its integrity.
  • hSPT20 and hSAGA subunits are specifically recruited to genes activated by endoplasmic reticulum (ER) stress, along with RNA polymerase II.
  • Knockdown of hSPT20 impairs the cellular response to ER stress.
  • hSPT20 recruitment was not observed for genes induced by other stress types.

Conclusions:

  • hSPT20 is a critical component of the hSAGA complex, essential for its stability.
  • The hSAGA complex plays a direct and specific role in the transcriptional activation of ER stress-responsive genes.
  • hSAGA's regulation of stress-responsive genes is dependent on the type of stress encountered.

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