A screen for histone mutations that affect quiescence in S. cerevisiae

Abstract

Quiescence or G0 is a reversible state in which cells cease division but retain the ability to resume proliferation. Quiescence occurs in all organisms and is essential for stem cell maintenance and tissue renewal. It is also related to chronological lifespan (CLS)—the survival of postmitotic quiescent cells (Q cells) over time—and thus contributes to longevity. Important questions remain regarding the mechanisms that control entry into quiescence, maintenance of quiescence and re‐entry of Q cells into the cell cycle. S. cerevisiae has emerged as an excellent organism in which to address these questions because of the ease in which Q cells can be isolated. Following entry into G0, yeast cells remain viable for an extended period and can re‐enter the cell cycle when exposed to growth‐promoting signals. Histone acetylation is lost during the formation of Q cells and chromatin becomes highly condensed. This unique chromatin landscape regulates quiescence‐specific transcriptional repression and has been linked to the formation and maintenance of Q cells. To ask whether other chromatin features regulate quiescence, we conducted two comprehensive screens of histone H3 and H4 mutants and identified mutants that show either altered quiescence entry or CLS. Examination of several quiescence entry mutants found that none of the mutants retain histone acetylation in Q cells but show differences in chromatin condensation. A comparison of H3 and H4 mutants with altered CLS to those with altered quiescence entry found that chromatin plays both overlapping and independent roles in the continuum of the quiescence program.