Surface condensation of a pioneer transcription factor on DNA*

Transcription factors cluster into sub-micrometer sized condensates while initiating transcription of their target genes. How do cells achieve a liquid phase of constrained size and location that emerge at a finely tuned concentration is not known. Here we investigate the role of DNA in nucleation of condensates, using the pioneer transcription factor KLF-4. We show that KLF-4 forms liquid-like condensates on the DNA surface at physiological concentrations, below the one required for Klf4 phase separation. We demonstrate that condensation occurs via a switch-like transition from a thin adsorbed layer to a thick condensed layer on DNA that is well described as a prewetting transition on a heterogeneous substrate. This phenomena is thus a form of surface condensation mediated by and limited to the DNA surface.