DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions
DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions
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DOI：
10.1038/s41598-020-58093-5
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发表时间：
2020-01-24
影响因子：
4.6
通讯作者：
Young, David A.
中科院分区：
文献类型：
--
作者：
Barter, Matt J.;Bui, Catherine;Young, David A.
转录的调节以细胞类型特异性的方式发生，由包括DNA甲基化的表观遗传机制协调。甲基化变化也可能在干细胞分化过程中的谱系特化中发挥关键作用。为了进一步了解软骨细胞的表观遗传调控，我们通过Infinium 450 K甲基化阵列表征了间充质干细胞（MSCs）软骨形成过程中的DNA甲基化变化。在软骨形成分化过程中发现了显著的DNA低甲基化，包括许多关键软骨基因位点的变化。与软骨形成基因表达数据的整合揭示了上调基因中显著CpG的富集，而显著CpG位点的表征表明其主要定位于增强子区域。与其他组织（包括健康和患病的成人软骨）的甲基化谱进行比较，确定了软骨细胞特异性低甲基化区域以及骨关节炎中与差异甲基化CpG的重叠。总之，我们将DNA甲基化水平与软骨细胞表型相关联。其结果具有改善软骨生成以用于组织工程目的的潜力，并且还为观察到的软骨疾病如骨关节炎中的甲基化变化提供背景。
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.