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A New Model for Single-Molecule Tracking Analysis of Transcription Factor Dynamics

By David A Garcia, Gregory Fettweis, Diego M Presman, Ville Paakinaho, Christopher Jarzynski, Arpita Upadhyaya, Gordon L Hager

Posted 14 May 2019
bioRxiv DOI: 10.1101/637355

Single-molecule tracking allows the study of transcription factor dynamics in the nucleus, giving important information regarding the search and binding behavior of these proteins with chromatin in vivo. However, these experiments suffer from limitations due to photobleaching of the tracked protein and assumptions about the exponential behavior required for data interpretation, potentially leading to serious artifacts. Here, we developed an improved method to account for photobleaching effects, theory-based models to accurately describe transcription factor dynamics, and an unbiased model selection approach to determine the best predicting model. A new biological interpretation of transcriptional regulation emerges from the proposed models wherein transcription factor searching and binding on the DNA results in a broad distribution of binding affinities and accounts for the power-law behavior of transcription factor residence times.

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