Chromatin-mediated regulation of nucleolar structure and RNA Pol I localization by TOR

Chi Kwan Tsang, Paula G. Bertram, Wandong Ai, Ryan Drenan, X. F Steven Zheng

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

The target of rapamycin (TOR) protein is a conserved regulator of ribosome biogenesis, an important process for cell growth and proliferation. However, how TOR is involved remains poorly understood. In this study, we find that rapamycin and nutrient starvation, conditions inhibiting TOR, lead to significant nucleolar size reduction in both yeast and mammalian cells. In yeast, this morphological change is accompanied by release of RNA polymerase I (Pol I) from the nucleolus and inhibition of ribosomal DNA (rDNA) transcription. We also present evidence that TOR regulates association of Rpd3-Sin3 histone deacetylase (HDAC) with rDNA chromatin, leading to site-specific deacetylation of histone H4. Moreover, histone H4 hypoacetylation mutations cause nucleolar size reduction and Pol I delocalization, while rpd3A and histone H4 hyperacetylation mutations block the nucleolar changes as a result of TOR inhibition. Taken together, our results suggest a chromatin-mediated mechanism by which TOR modulates nucleolar structure, RNA Pol I localization and rRNA gene expression in response to nutrient availability.

Original languageEnglish (US)
Pages (from-to)6045-6056
Number of pages12
JournalEMBO Journal
Volume22
Issue number22
DOIs
StatePublished - Nov 17 2003

Keywords

  • Histone deacetylase
  • Nucleolus
  • RDNA
  • RNA polymerase I
  • Target of rapamycin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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