Histone H3K27 Demethylase JMJD3 in Cooperation with NF-κB Regulates Keratinocyte Wound Healing

J Invest Dermatol. 2016 Apr;136(4):847-858. doi: 10.1016/j.jid.2015.11.029. Epub 2016 Jan 21.


Histone H3K27me3 demethylase JMJD3 has been shown to be involved in keratinocyte differentiation and wound healing. However, the exact molecular mechanism underlying JMJD3-mediated keratinocyte wound healing has not been fully elucidated. In this study, we report on the biological function of JMJD3 in keratinocyte wound healing using in vitro cell and in vivo animal models. Our results indicate that JMJD3 up-regulation and NF-κB activation occur in the region of the wound edge during keratinocyte wound healing. We also found that JMJD3 interacts with NF-κB, resulting in increased expression of the inflammatory, matrix metalloproteinase, and growth factor genes via demethylation of H3K27me3 at the gene promoters. Consistently, inactivation of JMJD3 or NF-κB resulted in aberrant keratinocyte wound healing. Our study suggests that regulation of JMJD3 may provide a new therapeutic intervention for treating the chronic skin wound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Gene Expression Regulation*
  • Gene Expression Regulation, Enzymologic
  • Histones / chemistry
  • Humans
  • Inflammation
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Keratinocytes / cytology
  • Keratinocytes / enzymology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B p50 Subunit / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Skin / metabolism
  • Wound Healing*


  • Histones
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • RNA, Small Interfering
  • Nfkb1 protein, mouse
  • Jumonji Domain-Containing Histone Demethylases
  • KDM6B protein, human
  • Kdm6b protein, mouse