Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response
| Autor: | Farid Alisafaei, G. V. Shivashankar, Doorgesh Sharma Jokhun, Karthik Damodaran, A.V. Radhakrishnan, Vivek B. Shenoy, Saradha Venkatachalapathy |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Compressive Strength Transcription Genetic Heterochromatin Cell Biology Histone Deacetylases Epigenesis Genetic Transcriptome Histones 03 medical and health sciences Mice Prophase medicine Animals Molecular Biology Cell Shape Tissue homeostasis Cell Nucleus Nuclear Functions Cell Biology Articles Actomyosin Fibroblasts HDAC3 Chromatin Assembly and Disassembly Chromatin Cell biology 030104 developmental biology medicine.anatomical_structure Acetylation NIH 3T3 Cells Muscle Contraction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Fibroblasts exhibit heterogeneous cell geometries in tissues and integrate both mechanical and biochemical signals in their local microenvironment to regulate genomic programs via chromatin remodelling. While in connective tissues fibroblasts experience tensile and compressive forces (CFs), the role of compressive forces in regulating cell behavior and, in particular, the impact of cell geometry in modulating transcriptional response to such extrinsic mechanical forces is unclear. Here 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 an increase in the heterochromatin content by initiating removal of acetylation marks on the histone tails. This suggests that, in response to CF, fibroblasts condense their chromatin and enter into a transcriptionally less active and quiescent states as also revealed by transcriptome analysis. On removal of CF, the alteration in chromatin condensation was reversed. We also present a quantitative model linking CF-dependent changes in actomyosin contractility leading to chromatin condensation. Further, transcriptome analysis also revealed that the transcriptional response of cells to CF was geometry dependent. Collectively, our results suggest that CFs induce chromatin condensation and geometry-dependent differential transcriptional response in fibroblasts that allows maintenance of tissue homeostasis. |
| Databáze: | OpenAIRE |
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