title: Survival in Quiescence Requires the Euchromatic Deployment of Clr4/SUV39H by Argonaute-Associated Small RNAs.
abstract: Quiescence (G0) is a ubiquitous stress response through which cells enter reversible dormancy, acquiring distinct properties including reduced metabolism, resistance to stress, and long life. G0 entry involves dramatic changes to chromatin and transcription of cells, but the mechanisms coordinating these processes remain poorly understood. Using the fission yeast, here, we track G0-associated chromatin and transcriptional changes temporally and show that as cells enter G0, their survival and global gene expression programs become increasingly dependent on Clr4/SUV39H, the sole histone H3 lysine 9 (H3K9) methyltransferase, and RNAi proteins. Notably, G0 entry results in RNAi-dependent H3K9 methylation of several euchromatic pockets, prior to which Argonaute1-associated small RNAs from these regions emerge. Overall, our data reveal another function for constitutive heterochromatin proteins (the establishment of the global G0 transcriptional program) and suggest that stress-induced alterations in Argonaute-associated sRNAs can target the deployment of transcriptional regulatory proteins to specific sequences.
authors.affiliation: Massachusetts General Hospital Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Joh
authors.affiliation: Massachusetts General Hospital Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Jasbeer S
authors.initials: JS
authors.lastname: Khanduja
authors.affiliation: Massachusetts General Hospital Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Isabel A
authors.initials: IA
authors.lastname: Calvo
authors.affiliation: Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Meeta
authors.initials: M
authors.lastname: Mistry
authors.affiliation: Massachusetts General Hospital Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Palmieri
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Andrej J
authors.initials: AJ
authors.lastname: Savol
authors.affiliation: Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Shannan J
authors.initials: SJ
authors.lastname: Ho Sui
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ruslan I
authors.initials: RI
authors.lastname: Sadreyev
authors.affiliation: Massachusetts General Hospital Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Aryee
authors.affiliation: Massachusetts General Hospital Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: mmotamedi@hms.harvard.edu.
authors.forename: Mo
authors.initials: M
authors.lastname: Motamedi
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D022041:Euchromatin / Q000378:metabolism* / Q000648:ultrastructure; D015966:Gene Expression Regulation, Fungal; D006570:Heterochromatin / Q000378:metabolism / Q000648:ultrastructure; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C481643:Ago1 protein, S pombe; D060565:Argonaute Proteins; D018797:Cell Cycle Proteins; D022041:Euchromatin; D006570:Heterochromatin; D006657:Histones; D034741:RNA, Small Interfering; D029702:Schizosaccharomyces pombe Proteins; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C112744:clr4 protein, S pombe
keywords: Argonaute; Clr4/Suv39H1; G0; H3K9me; RNAi; Schizosaccharomyces pombe; heterochromatin; nuclear exosome; quiescence; sRNA