Cell shape regulates global histone acetylation in human mammary epithelial cells

Johanne Le Beyec, Ren Xu, Sun Young Lee, Celeste M. Nelson, Aylin Rizki, Jordi Alcaraz, Mina J. Bissell

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


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 (lrECM), mammary epithelial cells round up and undergo global histone deacetylation, a process critical for their functional differentiation. However, it remains unclear whether lrECM-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 lrECM 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 lrECM or on micropatterns lacked these structures. Disruption of the actin cytoskeleton with cytochalasin D phenocopied the lrECM-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.

Original languageEnglish
Pages (from-to)3066-3075
Number of pages10
JournalExperimental Cell Research
Issue number14
StatePublished - Aug 15 2007


  • Cell morphology
  • Chromatin structure
  • Differentiation
  • Histone acetylation

ASJC Scopus subject areas

  • Cell Biology


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