期刊
EXPERIMENTAL CELL RESEARCH
卷 313, 期 14, 页码 3066-3075出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2007.04.022
关键词
cell morphology; chromatin structure; differentiation; histone acetylation
资金
- NCI NIH HHS [R37 CA064786, R01 CA064786-09, CA 57621, R01 CA057621, R01 CA064786, CA 64786] Funding Source: Medline
Extracellular matrix (ECM) regulates cell morphology and gene expression in vivo; these relationships are maintained in three-dimensional (3D) cultures of mammary epithelial cells. In the presence of laminin-rich ECM (IrECM), mammary epithelial cells round up and undergo global histone deacetylation, a process critical for their functional differentiation. However, it remains unclear whether IrECM-dependent cell rounding and global histone deacetylation are indeed part of a common physical-biochemical pathway. Using 3D cultures as well as nonadhesive and micropatterned substrata, here we showed that the cell 'rounding' caused by IrECM was sufficient to induce deacetylation of histones H3 and H4 in the absence of biochemical cues. Microarray and confocal analysis demonstrated that this deacetylation in 3D culture is associated with a global increase in chromatin condensation and a reduction in gene expression. Whereas cells cultured on plastic substrata formed prominent stress fibers, cells grown in 3D IrECM or on micropatterns lacked these structures. Disruption of the actin cytoskeleton with cytochalasin D phenocopied the IrECM-induced cell rounding and histone deacetylation. These results reveal a novel link between ECM-controlled cell shape and chromatin structure and suggest that this link is mediated by changes in the actin cytoskeleton. (c) 2007 Elsevier Inc. All rights reserved.
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