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SUMMARY:Simulating the binding of the pioneer transcription factor Oct4 to
  the nucleosome - Dr Jan Huertas\, Department of Chemistry\, University of
  Cambridge
DTSTART:20221205T140000Z
DTEND:20221205T143000Z
UID:TALK193369@talks.cam.ac.uk
CONTACT:Dr Venkat Kapil
DESCRIPTION:Transcription factors are proteins that bind to DNA to regulat
 e 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 pac
 ked regions of the genome\, where the DNA is wrapped around a nucleoprotei
 n complex called the nucleosome. \nOct4 is a pioneer transcription factor\
 , involved in pluripotency maintenance\, that can be used for reprogrammin
 g of adult cells into stem-cell like cells. Using experimental data\, we b
 uilt models of Oct4 bound to two different native nucleosomes. We then per
 formed over 50 µs of atomistic simulations of the Oct4-nucleosome complex
 es\, which we compared to 25µs of nucleosome alone simulations. We found 
 that nucleosome flexibility is a requirement for a multidomain transcripti
 on factor like Oct4 to bind. Furthermore\, we described two different mech
 anisms in which Oct4 can alter nucleosome dynamics\, either by stabilizing
  naturally occurring nucleosome opening events or inducing large opening e
 vents not seen in the nucleosome alone simulations. Overall\, our findings
  provide a mechanistic description of the effects of a pioneer transcripti
 on factor bound to a nucleosome\, at an unprecedented resolution. This wor
 k 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.
LOCATION:Zoom link: https://zoom.us/j/92447982065?pwd=RkhaYkM5VTZPZ3pYSHpt
 UXlRSkppQT09
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