title: Mitochondrial control through nutritionally regulated global histone H3 lysine-4 demethylation.
abstract: Histone demethylation by Jumonji-family proteins is coupled with the decarboxylation of α-ketoglutarate (αKG) to yield succinate, prompting hypotheses that their activities are responsive to levels of these metabolites in the cell. Consistent with this paradigm we show here that the Saccharomyces cerevisiae Jumonji demethylase Jhd2 opposes the accumulation of H3K4me3 in fermenting cells only when they are nutritionally manipulated to contain an elevated αKG/succinate ratio. We also find that Jhd2 opposes H3K4me3 in respiratory cells that do not exhibit such an elevated αKG/succinate ratio. While jhd2∆ caused only limited gene expression defects in fermenting cells, transcript profiling and physiological measurements show that JHD2 restricts mitochondrial respiratory capacity in cells grown in non-fermentable carbon in an H3K4me-dependent manner. In association with these phenotypes, we find that JHD2 limits yeast proliferative capacity under physiologically challenging conditions as measured by both replicative lifespan and colony growth on non-fermentable carbon. JHD2's impact on nutrient response may reflect an ancestral role of its gene family in mediating mitochondrial regulation.
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Soloveychik
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.
authors.forename: Mengshu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.|Terrence Donnelly Centre for Cellular &Biomolecular Research, University of Toronto, ON, M5S 3E1, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Zaslaver
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.
authors.forename: Kwanyin
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.
authors.forename: Ashrut
authors.initials: A
authors.lastname: Narula
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.
authors.forename: River
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.|Terrence Donnelly Centre for Cellular &Biomolecular Research, University of Toronto, ON, M5S 3E1, Canada.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Rosebrock
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.|Terrence Donnelly Centre for Cellular &Biomolecular Research, University of Toronto, ON, M5S 3E1, Canada.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Caudy
authors.affiliation: Department of Molecular Genetics, University of Toronto, ON, M5S 1A8, Canada.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Meneghini
mesh_terms: D004261:DNA Replication; D000073398:Demethylation; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D007656:Ketoglutaric Acids; D029701:Saccharomyces cerevisiae Proteins; D019802:Succinic Acid; C519119:JHD2 protein, S cerevisiae; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine