title: Acetyl-CoA induces transcription of the key G1 cyclin CLN3 to promote entry into the cell division cycle in Saccharomyces cerevisiae.
abstract: In budding yeast cells, nutrient repletion induces rapid exit from quiescence and entry into a round of growth and division. The G1 cyclin CLN3 is one of the earliest genes activated in response to nutrient repletion. Subsequent to its activation, hundreds of cell-cycle genes can then be expressed, including the cyclins CLN1/2 and CLB5/6. Although much is known regarding how CLN3 functions to activate downstream targets, the mechanism through which nutrients activate CLN3 transcription in the first place remains poorly understood. Here we show that a central metabolite of glucose catabolism, acetyl-CoA, induces CLN3 transcription by promoting the acetylation of histones present in its regulatory region. Increased rates of acetyl-CoA synthesis enable the Gcn5p-containing Spt-Ada-Gcn5-acetyltransferase transcriptional coactivator complex to catalyze histone acetylation at the CLN3 locus alongside ribosomal and other growth genes to promote entry into the cell division cycle.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Tu
mesh_terms: D000105:Acetyl Coenzyme A / Q000494:pharmacology*; D000107:Acetylation / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D056766:Cyclin G1 / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012269:Ribosomal Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: C079895:CLN3 protein, S cerevisiae; D056766:Cyclin G1; D016213:Cyclins; D006657:Histones; D046912:Multiprotein Complexes; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000105:Acetyl Coenzyme A; D005947:Glucose