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Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response
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| Zeitschriftentitel: | Molecular Biology of the Cell |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Molecular Biology of the Cell, 29, 2018, 25, S. 3039-3051 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Cell Biology (ASCB)
|
| Schlagwörter: |
| author_facet |
Damodaran, Karthik Venkatachalapathy, Saradha Alisafaei, Farid Radhakrishnan, A. V. Sharma Jokhun, Doorgesh Shenoy, Vivek B. Shivashankar, G. V. Damodaran, Karthik Venkatachalapathy, Saradha Alisafaei, Farid Radhakrishnan, A. V. Sharma Jokhun, Doorgesh Shenoy, Vivek B. Shivashankar, G. V. |
|---|---|
| author |
Damodaran, Karthik Venkatachalapathy, Saradha Alisafaei, Farid Radhakrishnan, A. V. Sharma Jokhun, Doorgesh Shenoy, Vivek B. Shivashankar, G. V. |
| spellingShingle |
Damodaran, Karthik Venkatachalapathy, Saradha Alisafaei, Farid Radhakrishnan, A. V. Sharma Jokhun, Doorgesh Shenoy, Vivek B. Shivashankar, G. V. Molecular Biology of the Cell Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response Cell Biology Molecular Biology |
| author_sort |
damodaran, karthik |
| spelling |
Damodaran, Karthik Venkatachalapathy, Saradha Alisafaei, Farid Radhakrishnan, A. V. Sharma Jokhun, Doorgesh Shenoy, Vivek B. Shivashankar, G. V. 1059-1524 1939-4586 American Society for Cell Biology (ASCB) Cell Biology Molecular Biology http://dx.doi.org/10.1091/mbc.e18-04-0256 <jats:p> 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. </jats:p> Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response Molecular Biology of the Cell |
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Molecular Biology of the Cell |
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| title |
Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_unstemmed |
Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_full |
Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_fullStr |
Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_full_unstemmed |
Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_short |
Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_sort |
compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| topic |
Cell Biology Molecular Biology |
| url |
http://dx.doi.org/10.1091/mbc.e18-04-0256 |
| publishDate |
2018 |
| physical |
3039-3051 |
| description |
<jats:p> 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. </jats:p> |
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| author | Damodaran, Karthik, Venkatachalapathy, Saradha, Alisafaei, Farid, Radhakrishnan, A. V., Sharma Jokhun, Doorgesh, Shenoy, Vivek B., Shivashankar, G. V. |
| author_facet | Damodaran, Karthik, Venkatachalapathy, Saradha, Alisafaei, Farid, Radhakrishnan, A. V., Sharma Jokhun, Doorgesh, Shenoy, Vivek B., Shivashankar, G. V., Damodaran, Karthik, Venkatachalapathy, Saradha, Alisafaei, Farid, Radhakrishnan, A. V., Sharma Jokhun, Doorgesh, Shenoy, Vivek B., Shivashankar, G. V. |
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| description | <jats:p> 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. </jats:p> |
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| imprint_str_mv | American Society for Cell Biology (ASCB), 2018 |
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| spelling | Damodaran, Karthik Venkatachalapathy, Saradha Alisafaei, Farid Radhakrishnan, A. V. Sharma Jokhun, Doorgesh Shenoy, Vivek B. Shivashankar, G. V. 1059-1524 1939-4586 American Society for Cell Biology (ASCB) Cell Biology Molecular Biology http://dx.doi.org/10.1091/mbc.e18-04-0256 <jats:p> 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. </jats:p> Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response Molecular Biology of the Cell |
| spellingShingle | Damodaran, Karthik, Venkatachalapathy, Saradha, Alisafaei, Farid, Radhakrishnan, A. V., Sharma Jokhun, Doorgesh, Shenoy, Vivek B., Shivashankar, G. V., Molecular Biology of the Cell, Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response, Cell Biology, Molecular Biology |
| title | Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_full | Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_fullStr | Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_full_unstemmed | Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_short | Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_sort | compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| title_unstemmed | Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response |
| topic | Cell Biology, Molecular Biology |
| url | http://dx.doi.org/10.1091/mbc.e18-04-0256 |