DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions
Autor: | Rodolfo Gómez, David Young, Hannah R Elliott, Louise N. Reynard, Andrew J. Skelton, Julia Falk, Matt J. Barter, Kathleen Cheung, Catherine Bui |
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Přispěvatelé: | Newcastle University [Newcastle], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), University of Bristol [Bristol] |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Cartilage Articular Adolescent Cellular differentiation lcsh:Medicine Bone Marrow Cells Biology Article 03 medical and health sciences Young Adult 0302 clinical medicine Chondrocytes Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Epigenetics Enhancer lcsh:Science Cells Cultured ComputingMilieux_MISCELLANEOUS Regulation of gene expression Cartilage development Multidisciplinary DNA methylation lcsh:R Mesenchymal Stem Cells Methylation Chondrogenesis Chromatin Cell biology 030104 developmental biology Enhancer Elements Genetic Gene Expression Regulation Organ Specificity lcsh:Q CpG Islands 030217 neurology & neurosurgery DNA hypomethylation |
Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2020, 10 (1), ⟨10.1038/s41598-020-58093-5⟩ Barter, M J, Bui, C, Cheung, K, Falk, J, Gómez, R, Skelton, A J, Elliott, H R, Reynard, L N & Young, D A 2020, ' DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions ', Scientific Reports, vol. 10, 1169 (2020) . https://doi.org/10.1038/s41598-020-58093-5 Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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