UV irradiation-induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines

Takaaki Yamada, Seiji Hasegawa, Yohei Iwata, Masaru Arima, Tsukane Kobayashi, Shigeki Numata, Satoru Nakata, Kazumitsu Sugiura, Hirohiko Akamatsu

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)723-729
Number of pages7
JournalExperimental Dermatology
Volume28
Issue number6
DOIs
Publication statusPublished - 01-06-2019

Fingerprint

Lentigo
5-Methylcytosine
Skin
Genes
Irradiation
Methylation
DNA
Catenins
Melanocytes
Methyltransferases
Stem cells
Stem Cells
Cells
Hyperpigmentation
Wnt Signaling Pathway
Cytosine
DNA Methylation
Gene expression
Epidermis
Cell Division

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Yamada, T., Hasegawa, S., Iwata, Y., Arima, M., Kobayashi, T., Numata, S., ... Akamatsu, H. (2019). UV irradiation-induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines. Experimental Dermatology, 28(6), 723-729. https://doi.org/10.1111/exd.13949
Yamada, Takaaki ; Hasegawa, Seiji ; Iwata, Yohei ; Arima, Masaru ; Kobayashi, Tsukane ; Numata, Shigeki ; Nakata, Satoru ; Sugiura, Kazumitsu ; Akamatsu, Hirohiko. / UV irradiation-induced DNA hypomethylation around WNT1 gene : Implications for solar lentigines. In: Experimental Dermatology. 2019 ; Vol. 28, No. 6. pp. 723-729.
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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.",
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Yamada, T, Hasegawa, S, Iwata, Y, Arima, M, Kobayashi, T, Numata, S, Nakata, S, Sugiura, K & Akamatsu, H 2019, 'UV irradiation-induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines', Experimental Dermatology, vol. 28, no. 6, pp. 723-729. https://doi.org/10.1111/exd.13949

UV irradiation-induced DNA hypomethylation around WNT1 gene : Implications for solar lentigines. / Yamada, Takaaki; Hasegawa, Seiji; Iwata, Yohei; Arima, Masaru; Kobayashi, Tsukane; Numata, Shigeki; Nakata, Satoru; Sugiura, Kazumitsu; Akamatsu, Hirohiko.

In: Experimental Dermatology, Vol. 28, No. 6, 01.06.2019, p. 723-729.

Research output: Contribution to journalArticle

TY - JOUR

T1 - UV irradiation-induced DNA hypomethylation around WNT1 gene

T2 - Implications for solar lentigines

AU - Yamada, Takaaki

AU - Hasegawa, Seiji

AU - Iwata, Yohei

AU - Arima, Masaru

AU - Kobayashi, Tsukane

AU - Numata, Shigeki

AU - Nakata, Satoru

AU - Sugiura, Kazumitsu

AU - Akamatsu, Hirohiko

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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