Support us

Transcription dynamics in single cells

Regulation of transcription (copying of a gene’s DNA) is essential for the normal growth and function of cells. In a single cell, transcription can show large fluctuations in activity over time, resulting in variability between cells in a population. Such variability can result in different cellular responses of individual cells, for example to drug treatment. Our lab uses and develops single-molecule imaging techniques to visualize individual protein and RNA molecules in living cells. Our goal is to understand the mechanisms of transcription variation and dynamics in single cells.


Gene expression is a tightly regulated process to ensure that genes are activated in the right cell at the right time. In the last half century, our knowledge of gene regulation has greatly advanced, but the majority of measurements come from large populations of cells. However, individual cells in a population can exhibit considerable variability in transcriptional responses, arising from the random collision of molecules. This stochastic gene expression variation can influence important cell fate decisions and can also contribute to heterogeneity in tumors. 

Our lab aims to understand the mechanistic basis of stochastic gene expression variation by studying dynamics of gene expression at the molecular level in single cells. We employ and develop cutting-edge single-molecule microscopy techniques to directly visualize the behavior of individual protein and RNA molecules in living cells. We are interested in every cellular component or process that may regulate transcription, including promoter and enhancer sequences, gene-specific transcription factors, chromatin regulators, 3D genome architecture, ncRNA transcription, and the binding kinetics of the transcriptional machinery to the DNA.

We combine our live-cell microscopy methods with biophysical, genetic, molecular biology and computational approaches in both yeast and mammalian model systems. Our ultimate goal is to understand the molecular mechanisms of transcription regulation in single cells, and how stochasticity in transcription modulates cell-to-cell variability and contributes to cancer progression.

The interplay between transcription factors, nucleosomes and transcriptional bursting

We have developed a novel single-molecule imaging platform to directly visualize both transcription binding dynamics and transcriptional output in the same cell. In combination with other in vitro and in vitro single-molecule imaging approaches, we were able to correlate the binding of the Gal4 transcription factor with the transcriptional bursting kinetics of the Gal4 target genes GAL3 and GAL10 in living yeast cells. We found that Gal4 dwell time sets the transcriptional burst size. Gal4 dwell time depends on the affinity of the binding site and is reduced by orders of magnitude by nucleosomes. Our data support a model in which multiple RNA polymerases initiate transcription during one burst as long as the transcription factor is bound to DNA, and bursts terminate upon transcription factor dissociation.

Read the full story.

This site uses cookies

This website uses cookies to ensure you get the best experience on our website.