Single-molecule imaging of the transcription factor SRF reveals prolonged chromatin-binding kinetics upon cell stimulation
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- Lisa Hipp
- Institute of Physiological Chemistry, Ulm University, 89081 Ulm, Germany;
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- Judith Beer
- Institute of Physiological Chemistry, Ulm University, 89081 Ulm, Germany;
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- Oliver Kuchler
- Institute of Physiological Chemistry, Ulm University, 89081 Ulm, Germany;
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- Matthias Reisser
- Institute of Biophysics, Ulm University, 89081 Ulm, Germany
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- Daniela Sinske
- Institute of Physiological Chemistry, Ulm University, 89081 Ulm, Germany;
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- Jens Michaelis
- Institute of Biophysics, Ulm University, 89081 Ulm, Germany
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- J. Christof M. Gebhardt
- Institute of Biophysics, Ulm University, 89081 Ulm, Germany
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- Bernd Knöll
- Institute of Physiological Chemistry, Ulm University, 89081 Ulm, Germany;
抄録
<jats:title>Significance</jats:title> <jats:p>How transcription factors (TFs) activate transcription is a long-standing but still unsolved question. We analyzed serum response factor (SRF), a stimulus-responsive TF mediating immediate early gene (IEG) and cytoskeletal gene expression at single-molecule resolution. Cell stimulation enhanced SRF activity by increasing the number of long chromatin-associated SRF molecules in an oscillating pattern. Further, stimulation enhanced the SRF chromatin residence time, and SRF binding events segregated into three distinct residence time regimes (short, intermediate, and long bound). In summary, our single-molecule imaging study reveals highly dynamic and diverse SRF interactions with DNA. Thus, cell stimulation regulates TF activity by several interconnected mechanisms including nucleus−cytoplasm shuttling, TF phosphorylation, cofactor recruitment, and extension of chromatin residence time and enhancing chromatin-bound TF numbers.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 116 (3), 880-889, 2018-12-31
Proceedings of the National Academy of Sciences