4.6 Article

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

Journal

EXPERIMENTAL DERMATOLOGY
Volume 30, Issue 8, Pages 1023-1032

Publisher

WILEY
DOI: 10.1111/exd.14153

Keywords

DNA methylation; epidermal differentiation; keratinocyte; methylationEPIC beadchip array; TRIM29

Categories

Funding

  1. ZonMw [821.02.013, 91616054]
  2. Radboud Institute for Molecular Life Sciences
  3. Chinese Scholarship Council grant [201406330059]

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This study aimed to assess the role of DNA methylation changes in regulating keratinocyte fate. The results suggest that in our in vitro experimental setup, changes in DNA methylation are unlikely to play a significant regulatory role in terminal keratinocyte differentiation.
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 theTRIM29gene. AlthoughTRIM29knock-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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