Date and Location
Tuesday, November 12, 2019, 11 am, 37 Convent Drive, Bethesda MD 20892; NIH, Bldg 37; Rm 4107/4041
Speaker: Dr. David Garcia-Grisales
(NIH/NCI; U. Maryland)
Title: “New Emergent Properties of Transcription Factor Dynamics and Their Interactions with Chromatin”
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 traced protein and pre-assumptions on 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 and nuclear microenvironment heterogeneity result in a broad distribution of binding affinities and accounts for the power-law behavior of transcription factor residence times. Moreover, two types of confinement are discovered; one related with specific DNA interaction and a second one related to liquid-liquid phase separation. The latter shows the importance of phase separation in transcriptional regulation and gene expression.
D. A. Garcia, G. Fettweis, D. M. Presman, V. Paakinakho, Ch. Jarzynski, A. Upadhyaya, G. L. Hager. A new model for single-molecule tracking analysis of transcription factor dynamics. 2019. BioRxiv doi: https://doi.org/10.1101/637355