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DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions

Lookup NU author(s): Dr Matthew Barter, Dr Catherine Bui, Kat Cheung, Julia Falk, Dr Rodolfo Gomez, Dr Hannah Elliott, Dr Louise Reynard, Professor David YoungORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Regulation of transcription occurs in a cell type specific manner orchestrated by epigenetic mechanisms including DNA methylation. Methylation changes may also play a key role in lineage specification during stem cell differentiation. To further our understanding of epigenetic regulation in chondrocytes we characterised the DNA methylation changes during chondrogenesis of mesenchymal stem cells (MSCs) by Infinium 450 K methylation array. Significant DNA hypomethylation was identified during chondrogenic differentiation including changes at many key cartilage gene loci. Integration with chondrogenesis gene expression data revealed an enrichment of significant CpGs in upregulated genes, while characterisation of significant CpG loci indicated their predominant localisation to enhancer regions. Comparison with methylation profiles of other tissues, including healthy and diseased adult cartilage, identified chondrocyte-specific regions of hypomethylation and the overlap with differentially methylated CpGs in osteoarthritis. Taken together we have associated DNA methylation levels with the chondrocyte phenotype. The consequences of which has potential to improve cartilage generation for tissue engineering purposes and also to provide context for observed methylation changes in cartilage diseases such as osteoarthritis.

Publication metadata

Author(s): Barter MJ, Bui C, Cheung K, Falk J, Gomez R, Skelton AJ, Elliott HR, Reynard LN, Young DA

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2020

Volume: 10

Issue: 10

Online publication date: 24/01/2020

Acceptance date: 21/12/2019

Date deposited: 24/01/2020

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/s41598-020-58093-5


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Funder referenceFunder name
JXR 10641
R476/0516Dunhill Medical Trust