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Curr Biol. 2013 Sep 9;23(17):1638-48. doi: 10.1016/j.cub.2013.06.050. Epub 2013 Aug 22.

Gcn5 and sirtuins regulate acetylation of the ribosomal protein transcription factor Ifh1.

Author information

1
Department of Biochemistry and Biophysics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 3(rd) Street, San Francisco, CA 94158, USA.

Abstract

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.

PMID:
23973296
PMCID:
PMC3982851
DOI:
10.1016/j.cub.2013.06.050
[Indexed for MEDLINE]
Free PMC Article

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