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SUMMARY:How do forces transmitted from a cell's environment affect DNA org
 anization? - Vivek  Shenoy (University of Pennsylvania)
DTSTART:20231212T150000Z
DTEND:20231212T160000Z
UID:TALK208540@talks.cam.ac.uk
DESCRIPTION:Microscale changes in tissue environment are translated to cha
 nges in cell behavior and phenotype\, yet the mechanisms behind how these 
 phenotypic changes occur are poorly understood. Here\, we describe and mod
 el chromatin\, which stores genetic information within the cell nucleus\, 
 as a dynamic nanomaterial whose configuration is modulated by chemo-mechan
 ical cues in the microenvironment. Our findings indicate that physiologic 
 chemo-mechanical cues can directly regulate chromatin architecture in prog
 enitor cell populations. Through direct experimental observation and model
 ing that incorporates phase transitions and histone methylation kinetics\,
  we demonstrate that soft environmental cues drive chromatin relocalizatio
 n to the nuclear boundary (leading to the formation of Lamin-Associated Do
 mains) and compaction. Conversely\, dynamic stiffening attenuates these ch
 anges. We show how methylation and acetylation impact the spatial distribu
 tion of the stiffness of the nucleus. Interestingly\, in diseased human fi
 brous tissue cells\, this link between mechanical inputs and chromatin nan
 o-scale remodeling is abrogated. These data indicate that chromatin dynami
 cs and plasticity may be hallmarks of disease progression and targets for 
 therapeutic intervention.
LOCATION:Seminar Room 2\, Newton Institute
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