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

Exp Dermatol. 2021 Aug;30(8):1023-1032. doi: 10.1111/exd.14153. Epub 2020 Jul 28.

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.

Keywords: DNA methylation; TRIM29; epidermal differentiation; keratinocyte; methylationEPIC beadchip array.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Differentiation / genetics*
  • DNA Methylation / genetics*
  • DNA-Binding Proteins / genetics
  • Epigenome / genetics*
  • Humans
  • Keratinocytes / metabolism*
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • TRIM29 protein, human
  • Transcription Factors