Open AccessMitochondrial control through nutritionally regulated global histone H3 lysine-4 demethylation
Author(s) -
M. Soloveychik,
Mengshu Xu,
Olga Zaslaver,
Kwanyin Lee,
Ashrut Narula,
River Jiang,
Adam P. Rosebrock,
Amy A. Caudy,
Marc D. Meneghini
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep37942
Subject(s) - h3k4me3 , demethylation , histone , lysine , demethylase , biology , histone h3 , histone methylation , biochemistry , gene expression , gene , phenotype , yeast , histone methyltransferase , microbiology and biotechnology , amino acid , dna methylation , promoter
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.