Lise Meitner Research Group
The main goal of our research is to elucidate the principles that govern quantitative gene control in mammals. We investigate how multiple quantitative signals are decoded by gene-regulatory networks and cis-regulatory landscapes to precisely control gene expression. We use the Xist gene as a model, which is upregulated during early development from one X chromosome in female mammals to initiate X-chromosome inactivation. The Xist regulatory network senses a two-fold expression difference of X-linked genes between the sexes, integrates information on X-dosage and differentiation and maintains two distinct Xist expression states within the same nucleus. This model thus allows us to investigate (1) how quantitative information is decoded, (2) how multiple signals are integrated, and (3) how distinct transcriptional states are maintained through epigenetic memory.
To analyze Xist regulation we use mouse embryonic stem cells, which allow us to model the onset of X-chromosome inactivation in cell culture. To dissect the underlying regulatory principles we integrate theoretical approaches, such as mathematical modelling, with experimental techniques, such as (epi)genomic profiling, CRISPR screens and (epi)genome engineering. We are also expanding existing tools to dissect functional interactions within gene-regulatory networks and to enable quantitative perturbations of endogenous genes. Recently, we have started to use synthetic biology approaches in some of our projects.