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Title 

Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells

Authors 

Kyung Sook YuJi Yoon JoSu Jin KimY LeeJ H BaeY H ChungSang Seok Koh

Publisher 

Elsevier

Issue Date 

2011

Citation 

Biochemical and Biophysical Research Communications, vol. 408, no. 1, pp. 160-166

Keywords 

ApoptosisDNA methylationElafinEpigeneticsFoxa2Melanoma

Abstract 

Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2011.04.001

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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