Glycolysis regulates gene expression by promoting the crosstalk between H3K4 trimethylation and H3K14 acetylation in Saccharomyces cerevisiae

Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth.However,how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains largely unknown.Here,we report that glucose specifically induces histone H3K4 trimethylation(H3K4me3),an evolutionarily conserved histone covalent modification associated with active gene transcription,and that glycolytic enzymes and metabolites are required for this in?duction.Although glycolysis supplies S-adenosylmethionine for histone methyltransferase Setl to catalyze H3K4me3,glucose induces H3K4me3 primarily by inhibiting histone demethylase Jhd2-catalyzed H3K4 demethylation.Glycolysis provides acetyl-CoA to stimulate histone acetyltransferase Gcn5 to acetylate H3K14,which then inhibits the binding of Jhd2 to chromatin to increase H3K4me3.By repressing Jhd2-mediated H3K4 demethylation,glycolytic enzymes regulate gene expression and cell survival during chronological aging.Thus,our results elucidate how cells reprogram their gene expression programs in response to glucose availability via histone modifications.

MOCS2 links nucleotide metabolism to nucleoli function

Dear Editor,Three polyamines,putrescine,spermidine,and spermine,are tightly regulated and are synthesized from arginine,ornithine,and methionine(Miller-Fleming et al.,2015;Figure 1A).Polyamine levels are increased in the red blood cells of amyotrophic lateral sclerosis and Parkinson’s disease(PD)patients(Miller-Fleming et al.,2015).Sulfur amino acid catabolism regulated by the molybdopterin synthase associating complex prevents onset of early events in PD and Alzheimer’s disease(Suganuma et al.,2018).MPT synthase,a heterodimer of MOCS2A and MOCS2B encoded by MOCS2,is essential for the biosynthesis of molybdenum cofactor(Moco).

Reading and Interpreting the Histone Acylation Code

Decades of research has explored the epigenetic control of gene expression and the impact of histone post-translational modifications （PTMs）, such as acetylation, on chromatin remodel- ing. Indeed, the writers, readers, and erasers of lysine acetylation are increasingly well understood. Recent studies have added crotonylation, butyrylation, and propionylation to the types of acylations by which histones are modified, and identified the YEATS protein domain as a critical reader of crotonylation. Now, Haitao Li, David Allis, and their col- leagues expand the scope of protein domains capable of read- ing crotonyl-lysine （Kcr） to include double PHD finger （DPF） domains. Importantly, the mechanism through which these domains recognize Kcr is quite distinct from their recognition by the YEATS domain [1]. In this highlight, we discuss recognition of acylated histones by the bromodomain （BRD）, the YEATS domain, and PHD fingers. We contrast the structural basis for their recognition of histones modified by acetylation and more recently discovered histone crotonylation [2-6].