(651g) Bursty Gene Transcription: Origins and Consequences

At many genes, transcription of mRNA appears to occur in random, intermittent bursts. The statistics of mRNA expression can be described by two parameters: the frequency at which bursts occur (burst frequency) and the average number of mRNA produced within each burst (burst size). The mean steady-state abundance of mRNA (and protein) is (proportional to) the product of the burst size and burst frequency. While it is widely known that transcriptional activators increase mean abundance, it remains unclear whether they do so by influencing burst size and/or burst frequency. Using single molecule mRNA measurements in budding yeast, we show that activators can affect both burst size and burst frequency, at varying thresholds that depend on the properties of the promoter. We present theoretical results that predict how different mixing of burst size and frequency regulation can lead to more bimodal or more graded responses of genes in positive feedback loops. Finally, we discuss how burst statistics might be regulated mechanistically through the processes of transcriptional initiation and reinitiation.