Transcription of the pain-related TRPV1 gene requires Runx1 and C/EBPβ factors

J Cell Physiol. 2013 Apr;228(4):860-70. doi: 10.1002/jcp.24236.

Abstract

Transient Receptor Potential Vanilloid type 1 channel (TRPV1) is an important endogenous transducer of noxious heat and chemical stimuli and is required during development of inflammatory hypersensitivity. The transcription factor Runx1 is known to play a relevant role in sensory neuron differentiation as it controls the expression of several sensory nociceptive receptors, including TRPV1. Here, we show that Runx1 up-regulates TRPV1 transcription activity by interacting directly with the proximal TRPV1 gene promoter sequence. Importantly, C/EBPβ a well-established heterodimer partner of Runx1 also binds to the TRPV1 promoter and cooperates with Runx1 to further stimulate TRPV1 transcription. Our results support a mechanism where Runx1-C/EBPβ-containing transcription regulatory complexes are recruited to the TRPV1 gene promoter to modulate TRPV1 expression in dorsal root ganglia neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Ganglia, Spinal / metabolism
  • Neurons / metabolism
  • PC12 Cells
  • Pain / genetics*
  • Pain / metabolism
  • Promoter Regions, Genetic
  • Rats
  • TRPV Cation Channels / biosynthesis
  • TRPV Cation Channels / genetics*
  • TRPV Cation Channels / metabolism
  • Transcription, Genetic
  • Transcriptional Activation
  • Up-Regulation

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Core Binding Factor Alpha 2 Subunit
  • Runx1 protein, rat
  • TRPV Cation Channels
  • Trpv1 protein, rat