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Mechanobiology of Disease
Poster Abstracts
104
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.