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


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.

SUBMITTER: Smits JPH 

PROVIDER: S-EPMC8359404 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Smits Jos P H JPH   Dirks René A M RAM   Qu Jieqiong J   Oortveld Merel A W MAW   Brinkman Arie B AB   Zeeuwen Patrick L J M PLJM   Schalkwijk Joost J   Zhou Huiqing H   Marks Hendrik H   van den Bogaard Ellen H EH  

Experimental dermatology 20200728 8


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 MethylationEP  ...[more]

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