Abstract draft for Q-bio

Quantitative measurements of transcription in single cells have demonstrated a high degree of stochastic variation among clonal cells in copy number of mRNA and protein, resulting from the bursts of molecule synthesis.  These experiments have raised the question of how metazoan systems cope with such intrinsic noise.  The gene regulatory networks which control the process of development across whole fields of cells in concentration dependent manners should be especially susceptible to this noise.   We have developed methods to allow single mRNA counting in whole-mount Drosophila embryos to investigate the nature of expression noise for the key regulatory genes hunchback and snail.   We show the previously observed trade-off between speed of mRNA production and precision of production is avoided in these cells, and that these developmental regulatory genes can maximize both quantities simultaneously.  By measuring the lifetime of the transcribing state for these genes under (1) different concentrations of the activating factors and (2) different numbers of regulatory enhancers, we show evidence that the developmental transcription factors Bcd, Dorsal and Twi more strongly affect the rate of promoter priming than the rate of polymerase recruitment.  A general mathematical model of transcriptional regulation explains why this distinction allows the speed/precision tradeoff to be circumvented.   These results show the dominantly reported bursty nature of mRNA synthesis is avoided by the particular regulatory mechanisms used for developmental control genes, and provides a molecular basis for this distinction.