Abstract
BackgroundQuiescent cells have a low level of gene activity compared to growing cells. Using a yeast model for cellular quiescence, we defined the genome-wide profiles of three species of histone methylation associated with active transcription between growing and quiescent cells, and correlated these profiles with the presence of RNA polymerase II and transcripts.ResultsQuiescent cells retained histone methylations normally associated with transcriptionally active chromatin and had many transcripts in common with growing cells. Quiescent cells also contained significant levels of RNA polymerase II, but only low levels of the canonical initiating and elongating forms of the polymerase. The RNA polymerase II associated with genes in quiescent cells displayed a distinct occupancy profile compared to its pattern of occupancy across genes in actively growing cells. Although transcription is generally repressed in quiescent cells, analysis of individual genes identified a period of active transcription during the development of quiescence.ConclusionsThe data suggest that the transcript profile and histone methylation marks in quiescent cells were established both in growing cells and during the development of quiescence and then retained in these cells. Together, this might ensure that quiescent cells can rapidly adapt to a changing environment to resume growth.
Highlights
Quiescent cells have a low level of gene activity compared to growing cells
By following the transcription and histone methylation patterns on individual genes during the formation of quiescent cells, we found that at some genes the transcript and epigenetic profiles in mature quiescent cells were inherited from growing cells, while at other genes these profiles were established during early stages in the development of quiescent cells and retained in this cell population
In contrast to the global decrease in the levels of histone acetylation in both a mixed population of stationary phase cells [24] and in isolated quiescent cells (Additional file 1: Figure S1E) [16], the levels of H3K4 di-methylation (H3K4me2) and H3K36 di- and tri-methylation (H3K36me2, me3) were similar between log cells and purified Q and NQ cells (Fig. 1a; Additional file 1: Figure S1F). This is consistent with the report that these modified histones were present at high levels in unseparated stationary phase cells formed upon severe nutrient deprivation [24]
Summary
Quiescent cells have a low level of gene activity compared to growing cells. Using a yeast model for cellular quiescence, we defined the genome-wide profiles of three species of histone methylation associated with active transcription between growing and quiescent cells, and correlated these profiles with the presence of RNA polymerase II and transcripts. In quiescent adult stem cells, the promoters of many genes, even those not being actively transcribed, are marked with H3K4me, which is considered a permissive state for transcription [9, 10]. These studies have promoted the hypothesis that quiescence represents a poised state that enables rapid gene activation when G0 cells are stimulated to resume proliferation or to differentiate. The functional relationship between the transcription and epigenetic states of quiescent cells is not well defined It is not known how these states are established during the development of quiescent cells. This has allowed the analysis of the transcription and epigenetic profiles of quiescent cells to be defined over time in the absence of interference from the nonquiescent cell population [14,15,16]
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