Transcription factors (TFs) are proteins that play key roles in transcriptional control through binding to specific sequences on DNA. How TF concentration and binding site affinity shape the effect of TFs on target genes is not well understood. In this seminar I will present recent modelling work of the group addressing this problem.

First, I will discuss how varying the concentration of a TF may affect the transcription level of a gene without affecting the timing of gene activation.

Second, I will present recent work combining kinetic modelling, deep learning and experiments in mouse embryonic stem cells to understand how low-affinity TF binding sites impact chromatin accessibility. This is the result of a collaboration with the group of Julia Zeitlinger, which some of you may remember as one of our first sabbatical visitors.

Finally, I will move beyond models of a single gene towards a genomic-level view of regulation. Here, I will explain our efforts to model TFs binding to many sites in the genome and some of the functional consequences.

Together, these studies illustrate how mechanistic models of dose-response relationships can help decode the regulatory information of the genome.

Refs:

Ravanelli et al., PLOS Computational Biology, 2026

Weilert et al., Cell Genomics, 2026

Martinez-Corral et al., PNAS, 2024.

If you would like to attend the seminar, please register here.