Journal
CELL PROLIFERATION
Volume 52, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/cpr.12638
Keywords
differentiation; epidermis; Jarid1b; Ovol1; Ship1
Categories
Funding
- National Natural Science Foundation of China [81770978, 81701381, 81672662, 81774248] Funding Source: Medline
- the Natural Science Foundation of Shandong Province [ZR2014CM040] Funding Source: Medline
- Shandong Provincial Education Department Program [J14LK02] Funding Source: Medline
- the Shandong Medical and Health Science and Technology Development Plan [2016WS0268] Funding Source: Medline
- the Key Research and Development Program of Shandong Province [2017GSF18193, 2018GSF118012] Funding Source: Medline
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Objectives Terminally differentiated stratified squamous epithelial cells play an important role in barrier protection of the skin. The integrity of epidermal cells is maintained by tight regulation of proliferation and differentiation. The aim of this study was to investigate the role of epigenetic regulator H3K4me3 and its demethylase Jarid1b in the control of epithelial cell differentiation. Materials and methods RT-qPCR, Western blotting and IHC were used to detect mRNA and protein levels. We analysed cell proliferation by CCK8 assay and cell migration by wound healing assay. ChIP was used to measure H3K4me3 enrichment. A chamber graft model was established for epidermal development. Results Our studies showed that H3K4me3 was decreased during epidermal differentiation. The H3K4me3 demethylase Jarid1b positively controlled epidermal cell differentiation in vitro and in vivo. Mechanistically, we found that Jarid1b substantially increased the expression of mesenchymal-epithelial transition (MET)-related genes, among which Ovol1 positively regulated differentiation gene expression. In addition, Ovol1 expression was repressed by PI3K-AKT pathway inhibitors and overexpression (O/E) of the PI3K-AKT pathway suppressor Ship1. Knockdown (KD) of Ship1 activated downstream PI3K-AKT pathway and enhanced Ovol1 expression in HaCaT. Importantly, we found that Jarid1b negatively regulated Ship1 expression, but not that of Pten, by directly binding to its promoter to modulate H3K4me3 enrichment. Conclusion Our results identify an essential role of Jarid1b in the regulation of the Ship1/AKT/Ovol1 pathway to promote epithelial cell differentiation.
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