Power-law behavior of transcription factor dynamics at the single-molecule level implies a continuum affinity model

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

Nucleic Acids Research, gkab072, https://doi.org/10.1093/nar/gkab072

Transcription factors (TF) must engage with chromatin to regulate gene expression. Using single-molecule tracking, it is now possible to follow individual TF molecule tracks inside live cells. As the TF moves around the nucleus, it travels through a rugged energy landscape of binding affinities. Current interpretations of dwell times for transcription factors invoke a bi-exponential model, assuming that nonspecific interaction with chromatin corresponds to a fast component, while a slower component represents specific binding. In this study, investigators have shown that the bi-exponential model mis-represents the true interaction behavior of TFs. The authors first describe a rigorous treatment for photo-bleaching correction. Using this methodology, they find that transcription factor dwell time distributions are best described by a power-law model, and show how power-law distributions emerge as a result of a broad distribution of transcription factor-chromatin interaction affinities.

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