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journal article·2024-04-04Open access

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

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

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Abstract

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.
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Research context

OpenAlex topics: RNA Research and Splicing · RNA modifications and cancer · Genomics and Chromatin Dynamics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Signalling Research Centres BIOSS and CIBSS University of Freiburg Schänzlestraße 18 79104 Freiburg Germany

Faculty of Biology University of Freiburg Schänzlestraße 1 79104 Freiburg Germany

Spemann Graduate School of Biology and Medicine (SGBM) University of Freiburg Albertstraße 21a 79104 Freiburg Germany

INM – Leibniz Institute for New Materials Campus D2 2 66123 Saarbrücken Germany

Center for Bioinformatics Saarland Informatics Campus Saarland University 66123 Saarbrücken Germany

Synthetic Biology and Biomedical Engineering Laboratory Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 China

Biberach University of Applied Sciences Karlstraße 6–11 88400 Biberach an der Riß Germany

Department of Experimental Physics and Center for Biophysics Saarland University 66123 Saarbrücken Germany

Institute for Immunodeficiency Center for Chronic Immunodeficiency (CCI) Medical Center Faculty of Medicine University of Freiburg Breisacherstr. 115 79106 Freiburg Germany

CIBSS – Centre for Integrative Biological Signalling Studies University of Freiburg Schänzlestraße 18 79104 Freiburg Germany

DZIF – German Center for Infection Research Deutsches Zentrum für Infektionsforschung e.V. Inhoffenstr. 7 38124 Braunschweig Germany

RESIST – Cluster of Excellence 2155 to Hanover Medical School Medizinische Hochschule Hannover Carl‐Neuberg‐Str. 1 30625 Hannover Germany

Department of Materials Science and Engineering, Campus D2 2 Saarland University 66123 Saarbrücken Germany

Funding

National Natural Science Foundation of China · Deutsche Forschungsgemeinschaft

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