Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

15-POS Board 15 Compressive Force Induces Chromatin Compaction in a Reversible Manner by Reducing Actomyosin Contractility and Shuttling HDAC3 to the Nucleus. Karthik Damodaran 1,2 , Saradha Venkatachalapathy 1 , AV Radhakrishnan 1 , Doorgesh S. Jokhun 1 , GV Shivashankar 1,2,3 , 1 Mechanobiology Institute, National University of Singapore, Singapore, Singapore, 2 Department of Biological Sciences, National University of Singapore, Singapore, Singapore, 3 FIRC (Foundation for Italian Cancer Research) Institute of Molecular Oncology (IFOM), Milan, Italy. Fibroblasts, one of the major type of cells in connective tissue, experience compressive force (CF) in its local microenvironment. These CFs influence the behavior of fibroblasts by regulating their genomic programs. The genomic programs in cells could be regulated by altering their chromatin compaction states. How CF alters chromatin compaction states in fibroblasts is not well understood. In this study, we show that CF on geometrically well defined mouse fibroblast cells reduces actomyosin contractility and shuttles Histone Deacetylase 3 (HDAC3), into the nucleus. HDAC3 then triggers increase in heterochromatin content by initiating the first step of removing acetylation marks on the histone tails in the euchromatin region. These histone tails are then further modified and recruited into the heterochromatin. In addition to increase in heterochromatin content, there is also enrichment of Lamin A/C at the nuclear periphery. This suggests that, in response to CF, fibroblasts stiffen their nucleus and enter into quiescent state, which is also reflected at the transcription level. This process was found to be reversible suggesting an existence of structural memory in these fibroblasts. This study shows how fibroblasts maintain their homeostasis in response to CF, failing which, has major implications in pathological conditions.

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