Simulating the binding of the pioneer transcription factor Oct4 to the nucleosome

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• Dr Jan Huertas, Department of Chemistry, University of Cambridge
• Monday 05 December 2022, 14:00-14:30
• Zoom link: https://zoom.us/j/92447982065?pwd=RkhaYkM5VTZPZ3pYSHptUXlRSkppQT09.

If you have a question about this talk, please contact Dr Venkat Kapil.

Transcription factors are proteins that bind to DNA to regulate gene expression. Historically, DNA accessibility has been considered a prerequisite indispensable for transcription factor function. Nevertheless, in recent years certain transcription factors have been shown to have “pioneering activity”, meaning that they can bind specifically in packed regions of the genome, where the DNA is wrapped around a nucleoprotein complex called the nucleosome. Oct4 is a pioneer transcription factor, involved in pluripotency maintenance, that can be used for reprogramming of adult cells into stem-cell like cells. Using experimental data, we built models of Oct4 bound to two different native nucleosomes. We then performed over 50 µs of atomistic simulations of the Oct4-nucleosome complexes, which we compared to 25µs of nucleosome alone simulations. We found that nucleosome flexibility is a requirement for a multidomain transcription factor like Oct4 to bind. Furthermore, we described two different mechanisms in which Oct4 can alter nucleosome dynamics, either by stabilizing naturally occurring nucleosome opening events or inducing large opening events not seen in the nucleosome alone simulations. Overall, our findings provide a mechanistic description of the effects of a pioneer transcription factor bound to a nucleosome, at an unprecedented resolution. This work allows us to begin understanding the changes of genome architecture that happen upon expression and binding of certain transcription factors, and ultimately gives us the tools to understand cell-fate transitions.

This talk is part of the Lennard-Jones Centre series.

This talk is included in these lists:

• Hanchen DaDaDash
• Lennard-Jones Centre
• Zoom link: https://zoom.us/j/92447982065?pwd=RkhaYkM5VTZPZ3pYSHptUXlRSkppQT09

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