Terminal keratinocyte differentiation in vitro is associated with a stable DNA methylome

体外角质形成细胞终末分化与稳定的 DNA 甲基化组相关

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作者:Jos P H Smits, René A M Dirks, Jieqiong Qu, Merel A W Oortveld, Arie B Brinkman, Patrick L J M Zeeuwen, Joost Schalkwijk, Huiqing Zhou, Hendrik Marks, Ellen H van den Bogaard

Abstract

The epidermal compartment of the skin is regenerated constantly by proliferation of epidermal keratinocytes. Differentiation of a subset of these keratinocytes allows the epidermis to retain its barrier properties. Regulation of keratinocyte fate-whether to remain proliferative or terminally differentiate-is complex and not fully understood. The objective of our study was to assess if DNA methylation changes contribute to the regulation of keratinocyte fate. We employed genome-wide MethylationEPIC beadchip array measuring approximately 850 000 probes combined with RNA sequencing of in vitro cultured non-differentiated and terminally differentiated adult human primary keratinocytes. We did not observe a correlation between methylation status and transcriptome changes. Moreover, only two differentially methylated probes were detected, of which one was located in the TRIM29 gene. Although TRIM29 knock-down resulted in lower expression levels of terminal differentiation genes, these changes were minor. From these results, we conclude that-in our in vitro experimental setup-it is unlikely that changes in DNA methylation have an important regulatory role in terminal keratinocyte differentiation.

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