Epigenetic reprogramming during wound healing: loss of polycomb-mediated silencing may enable upregulation of repair genes.
Tissue repair is a complex process that requires wound-edge cells to proliferate and migrate, which in turn necessitates induction of a large repair transcriptome. Epigenetic modifications have emerged as crucial regulators of gene expression. Here, we ask whether epigenetic reprogramming might contribute to the concerted induction of repair genes by wound-edge cells. Polycomb group proteins (PcGs) co-operatively silence genes by laying down repressive marks such as histone H3 lysine 27 trimethylation (H3K27me3), which can be removed by specific demethylases. We show that PcGs Eed, Ezh2 and Suz12 are significantly downregulated during murine skin repair, whereas the newly described demethylases Jmjd3 and Utx are markedly upregulated. Correspondingly, we find a striking reduction of repressive H3K27me3 in the wound epidermis. Quantitative chromatin immunoprecipitation studies have revealed that there is less Eed bound to the regulatory regions of two paradigm wound-induced genes, Myc and Egfr, suggesting that loss of polycomb-mediated silencing might contribute to the induction of repair genes.
Shaw
Tanya
T
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK. tshaw@sgul.ac.uk
Martin
Paul
P
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D056484:Jumonji Domain-Containing Histone Demethylases; D008297:Male; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
C107275:Eed protein, mouse; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C494163:Suz12 protein, mouse; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C111778:Utx protein, mouse; C523761:Kdm6b protein, mouse; D010089:Oxidoreductases, N-Demethylating; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2