title: Histone methylation has dynamics distinct from those of histone acetylation in cell cycle reentry from quiescence.
abstract: Cell growth is attuned to nutrient availability to sustain homeostatic biosynthetic processes. In unfavorable environments, cells enter a nonproliferative state termed quiescence but rapidly return to the cell cycle once conditions support energetic needs. Changing cellular metabolite pools are proposed to directly alter the epigenome via histone acetylation. Here we studied the relationship between histone modification dynamics and the dramatic transcriptional changes that occur during nutrient-induced cell cycle reentry from quiescence in the yeast Saccharomyces cerevisiae. SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry showed that histone methylation-in contrast to histone acetylation-is surprisingly static during quiescence exit. Chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) revealed genome-wide shifts in histone acetylation at growth and stress genes as cells exit quiescence and transcription dramatically changes. Strikingly, however, the patterns of histone methylation remain intact. We conclude that the functions of histone methylation and acetylation are remarkably distinct during quiescence exit: acetylation rapidly responds to metabolic state, while methylation is independent. Thus, the initial burst of growth gene reactivation emerging from quiescence involves dramatic increases of histone acetylation but not of histone methylation.
authors.affiliation: Penn Epigenetics Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: Mews
authors.affiliation: Penn Epigenetics Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Zee
authors.affiliation: Penn Epigenetics Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Liu
authors.affiliation: Penn Epigenetics Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Donahue
authors.affiliation: Penn Epigenetics Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.affiliation: Penn Epigenetics Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA bergers@mail.med.upenn.edu.
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
mesh_terms: D000107:Acetylation; D000596:Amino Acids / Q000737:chemistry; D002265:Carboxylic Ester Hydrolases; D002453:Cell Cycle; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D016681:Genome, Fungal; D006657:Histones / Q000378:metabolism*; D007553:Isotope Labeling; D008745:Methylation; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013312:Stress, Physiological
chemical_list: D000596:Amino Acids; D002843:Chromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D002265:Carboxylic Ester Hydrolases; C042523:protein methylesterase