The tor pathway regulates gene expression by linking nutrient sensing to histone acetylation.
The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1 from RP gene promoters and leads to histone H4 deacetylation without affecting promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies Rpd3 as the major histone deacetylase responsible for reversing histone H4 acetylation at RP gene promoters in response to Tor inhibition by rapamycin or nutrient limitation. Our results illustrate that the Tor pathway links nutrient sensing with histone acetylation to control RP gene expression and cell growth.
Rohde
John R
JR
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cardenas
Maria E
ME
D000107:Acetylation; D000935:Antifungal Agents / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002843:Chromatin / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases; D006657:Histones / Q000378:metabolism*; D008957:Models, Genetic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism / Q000502:physiology*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D000089804:Shelterin Complex; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D034501:Telomere-Binding Proteins / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
D000935:Antifungal Agents; D002843:Chromatin; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D006657:Histones; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D020123:Sirolimus; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; C061886:ABF1 protein, S cerevisiae; C440829:RAP1 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae