title: Global Promoter Targeting of a Conserved Lysine Deacetylase for Transcriptional Shutoff during Quiescence Entry.
abstract: Quiescence is a conserved cell-cycle state characterized by cell-cycle arrest, increased stress resistance, enhanced longevity, and decreased transcriptional, translational, and metabolic output. Although quiescence plays essential roles in cell survival and normal differentiation, the molecular mechanisms leading to this state are not well understood. Here, we determined changes in the transcriptome and chromatin structure of S. cerevisiae upon quiescence entry. Our analyses revealed transcriptional shutoff that is far more robust than previously believed and an unprecedented global chromatin transition, which are tightly correlated. These changes require Rpd3 lysine deacetylase targeting to at least half of gene promoters via quiescence-specific transcription factors including Xbp1 and Stb3. Deletion of RPD3 prevents cells from establishing transcriptional quiescence, leading to defects in quiescence entry and shortening of chronological lifespan. Our results define a molecular mechanism for global reprogramming of transcriptome and chromatin structure for quiescence driven by a highly conserved chromatin regulator.
authors: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: Jeffrey N
authors: JN
authors: McKnight
authors: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: Joseph W
authors: JW
authors: Boerma
authors: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: lbreeden@fredhutch.org.
authors: Linda L
authors: LL
authors: Breeden
authors: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: ttsukiya@fredhutch.org.
authors: Toshio
authors: T
authors: Tsukiyama
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005800:Genes, Fungal; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D002843:Chromatin; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C523898:Stb3 protein, S cerevisiae; D015534:Trans-Activators; C108767:XBP1 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases