Current Biology
Volume 23, Issue 17, 9 September 2013, Pages 1638-1648
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Article
Gcn5 and Sirtuins Regulate Acetylation of the Ribosomal Protein Transcription Factor Ifh1

https://doi.org/10.1016/j.cub.2013.06.050Get rights and content
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Highlights

  • Ifh1 and Spt7 are highly acetylated proteins in yeast

  • Ifh1 is acetylated by Gcn5 and deacetylated by sirtuins

  • Acetylation of Ifh1 is inhibited by cell stress

  • Acetylation in an N-terminal domain inhibits Ifh1’s function as a transactivator

Summary

Background

In eukaryotes, ribosome biosynthesis involves the coordination of ribosomal RNA and ribosomal protein (RP) production. In S. cerevisiae, the regulation of ribosome biosynthesis occurs largely at the level of transcription. The transcription factor Ifh1 binds at RP genes and promotes their transcription when growth conditions are favorable. Although Ifh1 recruitment to RP genes has been characterized, little is known about the regulation of promoter-bound Ifh1.

Results

We used a novel whole-cell-extract screening approach to identify Spt7, a member of the SAGA transcription complex, and the RP transactivator Ifh1 as highly acetylated nonhistone species. We report that Ifh1 is modified by acetylation specifically in an N-terminal domain. These acetylations require the Gcn5 histone acetyltransferase and are reversed by the sirtuin deacetylases Hst1 and Sir2. Ifh1 acetylation is regulated by rapamycin treatment and stress and limits the ability of Ifh1 to act as a transactivator at RP genes.

Conclusions

Our data suggest a novel mechanism of regulation whereby Gcn5 functions to titrate the activity of Ifh1 following its recruitment to RP promoters to provide more than an all-or-nothing mode of transcriptional regulation. We provide insights into how the action of histone acetylation machineries converges with nutrient-sensing pathways to regulate important aspects of cell growth.

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