Mews P, Zee BM, Liu S, Donahue G, Garcia BA, Berger SL
Cell growth is attuned to nutrient availability to sustain homeostatic biosynthetic processes. In unfavorable environments, cells enter a non-proliferative 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 re-entry from quiescence in the yeast S. cerevisiae. SILAC-based mass spectrometry showed that histone methylation - in contrast to histone acetylation - is surprisingly static during quiescence exit. 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.