Mechanoregulation of h2-calponin gene expression and the role of notch signaling

Wen Rui Jiang, Geoffrey Cady, M. Moazzem Hossain, Qi Quan Huang, Xin Wang, J. P. Jin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The essential role of mechanical signals in regulating the function of living cells is universally observed. However, how mechanical signals are transduced in cells to regulate gene expression is largely unknown. We previously demonstrated that the gene encoding h2-calponin (Cnn2) is sensitively regulated by mechanical tension. In the present study, mouse genomic DNA containing the Cnn2 promoter was cloned, and a nested set of 5′ truncations was studied. Transcriptional activity of the Cnn2 promoter-reporter constructs was examined in transfected NIH/3T3, HEK293, and C2C12 cells for their responses to the stiffness of culture substrate. The results showed significant transcriptional activities of the -1.00- and -1.24-kb promoter constructs, whereas the -0.61-kb construct was inactive. The -1.38-, -1.57-, and -2.12-kb constructs showed higher transcriptional activity, whereas only the -1.57- and -2.12-kb constructs exhibited repression of expression when the host cells were cultured on low stiffness substrate. Internal deletion of the segment between -1.57 and -1.38 kb in the -2.12-kb promoter construct abolished the low substrate stiffness-induced repression. Site-specific deletion or mutation of an HES-1 transcription factor binding site in this region also abolished this repression effect. The level of HES-1 increased in cells cultured under a low tension condition, corresponding to the down-regulation of h2-calponin. h2-Calponin gene expression is further affected by the treatment of cells with Notch inhibitor and activator, suggesting an upstream signaling mechanism.

Original languageEnglish (US)
Pages (from-to)1617-1628
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number3
DOIs
StatePublished - Jan 17 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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