Histone Arginine Methylation-Mediated Epigenetic Regulation of Discoidin Domain Receptor 2 Controls the Senescence of Human Bone Marrow Mesenchymal Stem Cells

Figure 6

CARM1 regulated DDR2 expression through catalyzing H3R17 methylation in the DDR2 promoter region. (a) Specific inhibition of CARM1-mediated histone arginine methylation was achieved by treatment with 100 μM ellagic acid. CARM1 inhibition decreased DDR2 expression and increased p16 expression and led to the generation of a significant number of senescent cells. (b) ChIP results verified that CARM1 was capable of binding to the promoter region of DDR2 and preferentially methylated H3R17. In early-passage (P2) hBM-MSCs, clear coincidental CARM1 accumulation and H3R17 methylation on the DDR2 promoter region were identified, while no similar results were found in late-passage (P7) cells. (c) hBM-MSCs with CARM1 overexpression also showed similar coincidental CARM1 accumulation and H3R17 methylation, while those with CARM1 inhibition exhibited a significant decrease in CARM1 accumulation and H3R17 methylation. Bars represent the standard error of the from three repeats. Statistical significance was determined by ANOVA and Student’s -test. , .

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