Control of noise in gene expression. (360G-Wellcome-090904_Z_09_Z)

Stability and precision in gene expression are necessary to generate and maintain structure and function in biology. To understand these fundamental problems requires novel technologies to detect and measure transcription from single genes in real time. We have therefore developed a novel technology to visualise the transcriptional behaviour of single genes in individual living cells. We demonstrated that transcription is stochastic, characterised by irregular pulses of gene activity. But how is stochastic behaviour compatible with spatiotemporal precision and stability of gene expression? To address how stochastic pulsing generates precise spatial patterns of gene expression, and to distinguish between direct and feedback models of cell response, we will study pulsing during formation of a precise embryonic gene expression boundary. To determine origins of temporally precise gene expression, we will measure and entrain transcriptional cycling in single cells. To address how st ability of gene expression is regulated, we will use long term imaging to determine the extent to which transcriptional firing is maintained in cell lineages. We will address the role of chromatin in transcriptional memory. To define the regulators of transcriptional stability with unbiased approaches we will use FACS to purify mutants with high noise and low gene expression memory.