Global Promoter Targeting of a Conserved Lysine Deacetylase for Transcriptional Shutoff during Quiescence Entry

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. [Display omitted] •Dramatic reprogramming of transcription and chromatin accompany yeast quiescence•Rpd3 is required for quiescence entry, longevity, and transcriptional shutoff•Rpd3 targets at least half of genes via repressors upon quiescence entry•Rpd3 targeting distinguishes quiescence from starvation and the diauxic shift McKnight et al. demonstrate that widespread targeting of Rpd3, a highly conserved lysine deacetylase, is required for global reprogramming of transcription and chromatin structure in quiescent budding yeast. Rpd3-dependent reprogramming is essential for quiescence entry and longevity and distinguishes quiescence from other cell-cycle stages.