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Creating memories of transcription

Two genetically identical cells grown under the same conditions can exhibit stochastic fluctuations in gene expression. Such cell-to-cell variation in expression of key genes is hypothesized to help drive developmental fate decisions and cell specialization during differentiation. However, to date, most analyses dissecting steps involved in the activation of cell cycle or developmentally regulated promoters have been conducted using cell population-based assays, thereby precluding a detailed appreciation of how transcription factors, cofactors, and chromatin remodelers contribute to the stochastic nature of transcriptional activation in individual cells. In PNAS, Zhang et al. (1) conduct an elegant series of single cell pedigree analyses to explore molecular mechanisms influencing stochastic gene expression from the cell cycle-regulated HO promoter that drives cell fate decisions in Saccharomyces cerevisiae. Through the use of an unstable GFP reporter to visualize transcription indirectly, Zhang et al. demonstrate that different factors have independent modes by which they can regulate the HO promoter. Some factors primarily influence the frequency of transcriptional events or the fraction of cell cycles in which transcription from HO occurs, whereas others affect the amplitude or the level of expression from the HO promoter achieved within a given cell cycle. Assessing HO promoter activation at the single cell level has also permitted the authors to uncover evidence for a role of histone acetylation in conferring short-term cis-based memory of transcriptional states.