Back to Search
Start Over
UV irradiation‐induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines
- Source :
- Experimental Dermatology. 28:723-729
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Wnt/β-catenin signalling promotes melanogenesis in melanocytes and also induces melanocytogenesis from melanocyte stem cells (McSCs). Previous study reported that WNT1, a ligand which activates Wnt/β-catenin signalling pathway, was more highly expressed in the epidermis at SLs than in normal skin areas, suggesting that WNT1 causes hyperpigmentation. To elucidate the mechanism by which WNT1 expression is increased in SLs, we examined the methylation of 5-carbon of cytosine (5mC), that is 5-methylcytosine (5mC) level, in a region within the WNT1 promoter; the methylation of the region was known to negatively regulate WNT1 gene expression. We used an immortalized cell line of human interfollicular epidermal stem cells to analyse the effect of UVB irradiation on DNA methylation level of WNT1 promoter and found that UVB irradiation caused demethylation of WNT1 promoter and promoted WNT1 mRNA expression. It was also found that UVB irradiation reduced the expression of DNA methyltransferase 1 (DNMT1), an enzyme responsible for maintaining methylation patterns during cell division. Pathological analysis of SLs and non-SL regions in the human skin revealed that both DNMT1 expression and 5mC level were decreased at SLs compared to non-SL skins. Furthermore, bisulphite sequencing showed that the methylated CpG level in WNT1 promoter was also lower at SLs than in non-SL skins. Thus, in the skin exposed to a high amount of UV rays, excessive expression of WNT1 is thought to be caused by the demethylation of WNT1 promoter, and the upregulated WNT1 promotes melanocytogenesis and melanogenesis, then resulting in SL formation.
- Subjects :
- DNA (Cytosine-5-)-Methyltransferase 1
Keratinocytes
Male
0301 basic medicine
animal structures
Ultraviolet Rays
Biopsy
Bisulfite sequencing
Wnt1 Protein
Dermatology
Melanocyte
Biochemistry
DNA methyltransferase
Cell Line
030207 dermatology & venereal diseases
03 medical and health sciences
0302 clinical medicine
Gene expression
medicine
Humans
Epigenetics
RNA, Small Interfering
Molecular Biology
Aged
Skin
Hypopigmentation
Lentigo
integumentary system
Chemistry
Methylation
DNA Methylation
Middle Aged
Molecular biology
030104 developmental biology
medicine.anatomical_structure
Epidermal Cells
embryonic structures
DNA methylation
DNMT1
Melanocytes
CpG Islands
Female
Signal Transduction
Subjects
Details
- ISSN :
- 16000625 and 09066705
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Experimental Dermatology
- Accession number :
- edsair.doi.dedup.....20001edc126593173d6b7053ce86bbb4
- Full Text :
- https://doi.org/10.1111/exd.13949