Rpd3p relocation mediates a transcriptional response to rapamycin in yeast.
Treating yeast cells with rapamycin, a small molecule that inhibits the TOR proteins, leads to the repression of many genes. Consistent with prior studies, we find that RPD3, which encodes a histone deacetylase (HDAC), is required for repression upon rapamycin treatment. To elucidate the mechanism underlying RPD3-mediated repression, we screened all promoters in yeast for occupancy by Rpd3p before and after treatment with rapamycin. We find that Rpd3p binds to the promoters of rapamycin-repressible genes only following treatment. These data conflict with a previously proposed model suggesting that Rpd3p is constitutively bound to rapamycin-repressible genes and becomes active only after a stimulus such as treatment with rapamycin. Rather, the comprehensive analysis presented here strongly supports a model in which recruitment of Rpd3p to gene promoters is a regulated step in the control of gene repression.
Humphrey
Emily L
EL
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, 12 Oxford Street, Cambridge, MA 02138, USA.
Shamji
Alykhan F
AF
Bernstein
Bradley E
BE
Schreiber
Stuart L
SL
D015536:Down-Regulation / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005800:Genes, Fungal / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases; D020123:Sirolimus