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bioRxiv · 10.1101/2021.01.27.428421

Transcription activation is enhanced by multivalent interactions independent of liquid-liquid phase separation

Trojanowski, J.·Frank, L.·Rademacher, A.·Grigaitis, P.·Rippe, K.
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Abstract

Transcription factors (TFs) consist of a DNA binding and an activation domain (AD) that are considered to be independent and exchangeable modules. However, recent studies conclude that also the physico-chemical properties of the AD can control TF assembly at chromatin by driving a phase separation into transcriptional condensates. Here, we dissected transcription activation by comparing different synthetic TFs at a reporter gene array with real-time single-cell fluorescence microscopy readouts. In these experiments, binding site occupancy, residence time and co-activator recruitment in relation to multivalent TF interactions were compared. While phase separation propensity and activation strength of the AD were correlated, the actual formation of liquid-like TF droplets had a neutral or inhibitory effect on transcription activation. Rather, we conclude that multivalent AD mediated interactions increase the transcription activation capacity of a TF by stabilizing chromatin binding and mediating the recruitment of co-activators independent of phase separation.

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Trojanowski, J., Frank, L., Rademacher, A., Grigaitis, P., Rippe, K.. 2021-01-28. Transcription activation is enhanced by multivalent interactions independent of liquid-liquid phase separation. https://doi.org/10.1101/2021.01.27.428421

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