Biophysical Regulation of Histone Acetylation in Mesenchymal Stem Cells

Bioengineering College, Chongqing University, Chongqing, China.
Biophysical Journal (Impact Factor: 3.97). 04/2011; 100(8):1902-9. DOI: 10.1016/j.bpj.2011.03.008
Source: PubMed


Histone deacetylation and acetylation are catalyzed by histone deacetylase (HDAC) and histone acetyltransferase, respectively, which play important roles in the regulation of chromatin remodeling, gene expression, and cell functions. However, whether and how biophysical cues modulate HDAC activity and histone acetylation is not well understood. Here, we tested the hypothesis that microtopographic patterning and mechanical strain on the substrate regulate nuclear shape, HDAC activity, and histone acetylation. Bone marrow mesenchymal stem cells (MSCs) were cultured on elastic membranes patterned with parallel microgrooves 10 μm wide that kept MSCs aligned along the axis of the grooves. Compared with MSCs on an unpatterned substrate, MSCs on microgrooves had elongated nuclear shape, a decrease in HDAC activity, and an increase of histone acetylation. To investigate anisotropic mechanical sensing by MSCs, cells on the elastic micropatterned membranes were subjected to static uniaxial mechanical compression or stretch in the direction parallel or perpendicular to the microgrooves. Among the four types of loads, compression or stretch perpendicular to the microgrooves caused a decrease in HDAC activity, accompanied by the increase in histone acetylation and slight changes of nuclear shape. Knocking down nuclear matrix protein lamin A/C abolished mechanical strain-induced changes in HDAC activity. These results demonstrate that micropattern and mechanical strain on the substrate can modulate nuclear shape, HDAC activity, and histone acetylation in an anisotropic manner and that nuclear matrix mediates mechanotransduction. These findings reveal a new mechanism, to our knowledge, by which extracellular biophysical signals are translated into biochemical signaling events in the nucleus, and they will have significant impact in the area of mechanobiology and mechanotransduction.

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Available from: Xian Li, May 01, 2014
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    • "This reinforcement leads to decreased deflection to future mechanical stimuli, decreasing cellular sensitivity. While our data do not specifically connect acetylation with deflection, other groups have reported physical stimuli decreased HDAC6 activity and increased acetylation (Geiger et al., 2009; Li et al., 2011). Acetylation of tubulin has been implicated in microtubule stiffness (Felgner et al., 1996; Hawkins et al., 2013) and our results corroborate this. "
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    Preview · Article · Nov 2015 · Biology Open
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    • "Histone acetylation and deacetylation are critical to the modification of chromatin structure associated with the regulation of gene expression (21). Acetylation and deacetylation is involved in various developmental processes, including heart development. "
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    • "The results of these morphological studies suggest that the smaller 10 lm microgrooves were more effective in orienting VSC actin cytoskeleton and membrane protrusion parallel to the pattern direction. This result is consistent with previously reported results with other cell types cultured on similarly dimensioned microgroove surfaces [9] [13] [16]. "
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