A novel Gcn5p inhibitor represses cell growth, gene transcription and histone acetylation in budding yeast.
Histone acetyltransferases are key chromatin regulators responsible for transcriptional activation and cell cycle progression. We propose a simple yeast-based assay to determine the specificity and targets of novel Gcn5p inhibitors. Here, we report the finding of a novel, small molecule, MC1626, which is able to inhibit yeast cell growth, Gcn5p-dependent gene transcription and acetylation of the histone H3 N-terminal tail in vivo. Because HATs misregulation is invariably associated with human diseases, the identification of MC1626 as a novel cell-permeable Gcn5p inhibitor suggests that it may be a very useful starting tool for the further development of new molecules to be applied to expression profiling of genes regulated by histone H3 acetylation. In addition, our results demonstrate that MC1626 is a Gcn5p-dependent yeast growth inhibitor.
Ornaghi
Prisca
P
Dipartimento Genetica e Biologia Molecolare, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, I-00185 Roma, Italy.
Rotili
Dante
D
Sbardella
Gianluca
G
Mai
Antonello
A
Filetici
Patrizia
P
D000107:Acetylation; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006657:Histones / Q000378:metabolism*; D011494:Protein Kinases; D011804:Quinolines / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic / Q000187:drug effects*
D004268:DNA-Binding Proteins; D006657:Histones; C504219:MC1626; D011804:Quinolines; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases