Dresden 2026 – wissenschaftliches Programm
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DY: Fachverband Dynamik und Statistische Physik
DY 52: Statistical Physics of Biological Systems III (joint session BP/DY)
DY 52.6: Vortrag
Donnerstag, 12. März 2026, 16:15–16:30, BAR/SCHÖ
Thermodynamics of DNA sequence recognition by a transcription factor — •Jonas Neipel1,2,3, Anne Schwager1, Yahor Savich1,2,3, Douglas Diehl1, Anthony A. Hyman1, Frank Jülicher2,3, and Stephan W. Grill1,3 — 1Max Planck Institute for Molecular Cell Biology and Genetics, Dresden Germany — 2Max Planck Institute for the Physics of Complex Systems, Dresden Germany — 3Center for Systems Biology Dresden, Dresden, Germany
Transcription factors (TFs) are proteins that regulate the transcription of genes by binding to specific genomic positions defined by the DNA sequence. The sequence of preference of a TF is typically characterized by a single sequence motif that maximizes binding affinity. However, eukaryotic TFs bind to a spectrum of low affinity binding sites that vastly outnumber canonical motif sequences in the genome. Here, we develop an Ising model of DNA sequence recognition that yields quantitative prediction of TF binding energies across sequence space for the human TF KLF-4. The model is parametrized by in vitro experiments, where we quantify relative binding energies for various sequences in a competitive assay using fluorescence anisotropy. Strikingly, we find that the thus fully parametrized thermodynamic model quantitatively predicts KLF-4 occupancy across the human genome. Finally, we discuss how this genomic energy landscape guides the formation of TF condensates.
Keywords: Ising model; Transcription factors; Biomolecular condensates; DNA; Gene regulation