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|Title:||ROLE OF ACTIVE CYTOSKELETAL FORCES & NUCLEAR LAMINA IN REGULATING THE SPATIOTEMPORAL CHROMATIN ARCHITECTURE||Authors:||JOKHUN DOORGESH SHARMA||ORCID iD:||orcid.org/0000-0002-2974-8712||Keywords:||nuclear architecture, chromatin organization, nuclear & chromatin dynamics, active cytoskeleton, nuclear-based diagnostics, cell state classification||Issue Date:||1-Aug-2019||Citation:||JOKHUN DOORGESH SHARMA (2019-08-01). ROLE OF ACTIVE CYTOSKELETAL FORCES & NUCLEAR LAMINA IN REGULATING THE SPATIOTEMPORAL CHROMATIN ARCHITECTURE. ScholarBank@NUS Repository.||Abstract:||We investigated the intrinsically dynamic nature of the actin cytoskeleton as a means of relaying extracellular signals to the chromatin. We showed that the active cytoskeletal network continuously reorganizes and applies dynamic forces on the nucleus. Sampling local chromatin dynamics, we demonstrated that cytoskeletal fluctuations regulate the spatiotemporal chromatin architecture in an extracellular signal-dependent manner. We also showed that lamin A/C mechanically couples distal chromatin loci thereby limiting their movements and promoting correlated motion. We established that such changes in chromatin dynamics can modulate the binding kinetics of DNA binding proteins. Further, we underscored the link between chromatin organization and cellular state by demonstrating that a multivariate analysis of nuclear and chromatin architectural features efficiently classifies cells of different types. This thesis establishes chromatin organization as a hub for integrating extracellular signals while concurrently reflecting cellular state. Consequently, chromatin architecture can potentially serve as biomarker for novel image-based diagnostic platforms.||URI:||https://scholarbank.nus.edu.sg/handle/10635/164410|
|Appears in Collections:||Ph.D Theses (Open)|
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