Engineering Material Properties of Transcription Factor Condensates to Control Gene Expression in Mammalian Cells and Mice

Abstract: Phase separation of biomolecules into condensates is a key mechanism in the spatiotemporal organization of biochemical processes in cells. However, the impact of the material properties of biomolecular condensates on important processes, such as the control of gene expression, remains largely elusive. Here, the material properties of optogenetically induced transcription factor condensates are systematically tuned, and probed for their impact on the activation of target promoters. It is demonstrated that transcription factors in rather liquid condensates correlate with increased gene expression levels, whereas stiffer transcription factor condensates correlate with the opposite effect, reduced activation of gene expression. The broad nature of these findings is demonstrated in mammalian cells and mice, as well as by using different synthetic and natural transcription factors. These effects are observed for both transgenic and cell‐endogenous promoters. The findings provide a novel materials‐based layer in the control of gene expression, which opens novel opportunities in optogenetic engineering and synthetic biology.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Engineering Material Properties of Transcription Factor Condensates to Control Gene Expression in Mammalian Cells and Mice ; day:04 ; month:04 ; year:2024 ; extent:16
Small ; (04.04.2024) (gesamt 16)

Creator
Fischer, Alexandra A.M.
Robertson, Hanah B.
Kong, Deqiang
Grimm, Merlin M.
Grether, Jakob
Groth, Johanna
Baltes, Carsten
Fliegauf, Manfred
Lautenschläger, Franziska
Grimbacher, Bodo
Ye, Haifeng
Helms, Volkhard
Weber, Wilfried

DOI
10.1002/smll.202311834
URN
urn:nbn:de:101:1-2024040514150959085986
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:48 AM CEST

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