Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon

Mol Cell Biol. 2016 Mar 31;36(8):1297-309. doi: 10.1128/MCB.00950-15. Print 2016 Apr.


Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx(-/-) mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Deletion
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Mice, Inbred C57BL
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Physical Conditioning, Animal
  • Promoter Regions, Genetic
  • Rats
  • Rats, Wistar
  • Tendons / cytology
  • Tendons / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • Up-Regulation
  • Weight-Bearing


  • Gtf2ird1 protein, mouse
  • Homeodomain Proteins
  • Muscle Proteins
  • Nuclear Proteins
  • Trans-Activators
  • mohawk protein, mouse