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Transcription activation is enhanced by multivalent interactions independent of phase separation

Transcription factors (TFs) consist of a DNA-binding domain and an activation domain (AD) that are frequently considered to be independent and exchangeable modules. However, recent studies report that the physicochemical properties of the AD can control TF assembly at chromatin by driving phase sepa...

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Bibliographic Details
Main Authors: Trojanowski, Jorge (Author) , Frank, Lukas (Author) , Rademacher, Anne (Author) , Mücke, Norbert (Author) , Grigaitis, Pranas (Author) , Rippe, Karsten (Author)
Format: Article (Journal)
Language:English
Published: 19 May 2022
In: Molecular cell
Year: 2022, Volume: 82, Issue: 10, Pages: 1878-1893.e10
ISSN:1097-4164
DOI:10.1016/j.molcel.2022.04.017
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molcel.2022.04.017
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1097276522003288
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Author Notes:Jorge Trojanowski, Lukas Frank, Anne Rademacher, Norbert Mücke, Pranas Grigaitis, Karsten Rippe
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Summary:Transcription factors (TFs) consist of a DNA-binding domain and an activation domain (AD) that are frequently considered to be independent and exchangeable modules. However, recent studies report that the physicochemical properties of the AD can control TF assembly at chromatin by driving 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. In these experiments, binding site occupancy, residence time, and coactivator recruitment in relation to multivalent TF interactions were compared. While phase separation propensity and activation strength of the AD were linked, the actual formation of liquid-like TF droplets had a neutral or inhibitory effect on transcription activation. We conclude that multivalent AD-mediated interactions enhance the transcription activation capacity of a TF by increasing its residence time in the chromatin-bound state and facilitating the recruitment of coactivators independent of phase separation.
Item Description:Gesehen am 13.07.2022
Physical Description:Online Resource
ISSN:1097-4164
DOI:10.1016/j.molcel.2022.04.017

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