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表观遗传调控机制在脂肪细胞分化中发挥了重要的作用。为了研究DNA甲基转移酶Dnmt1在脂肪细胞分化中的作用,我们利用3T3-L1前脂肪细胞体外诱导分化模型,首先分析了该基因在脂肪细胞分化中的表达变化,发现Dnmt1的表达水平在分化起始阶段显著升高。如果在该过程中敲低Dnmt1的表达,则会显著影响细胞分化进程,抑制细胞脂质的生成。利用甲基化基因芯片分析,我们发现在分化起始阶段,Cdkn1a基因的启动子甲基化水平显著升高,并伴随基因表达水平的降低;而敲低Dnmt1的表达则能抑制Cdkn1a启动子的甲基化,提高基因的表达。这些研究结果表明,Dnmt1通过调控Cdkn1a启动子的甲基化,影响该基因的表达。进一步的研究发现,Dnmt1通过Cdkn1a启动子的甲基化调节脂肪细胞分化,表明Cdkn1a有可能在脂肪细胞分化、以及预防脂肪细胞增生中发挥关键的作用。
Epigenetic regulation mechanism plays an important role in adipocyte differentiation. In order to study the role of DNA methyltransferase Dnmt1 in adipocyte differentiation, we used the 3T3-L1 preadipocyte differentiation model in vitro, first analyzed the expression changes of this gene in adipocyte differentiation, and found that the expression level of Dnmt1 in differentiation The initial stage increased significantly. If we knocked down the expression of Dnmt1 in the process, it will significantly affect the process of cell differentiation and inhibit the formation of cellular lipids. Using methylation-based microarray analysis, we found that the promoter methylation of Cdkn1a gene was significantly increased along with the decrease of gene expression level at the initial stage of differentiation, while the knockdown of Dnmt1 expression inhibited the expression of Cdkn1a promoter Methylation enhances gene expression. These findings indicate that Dnmt1 affects the expression of Cdkn1a promoter through its methylation. Further studies found that Dnmt1 regulates adipocyte differentiation through the Cdkn1a promoter methylation, suggesting Cdkn1a may play a key role in adipocyte differentiation and preventing adipocyte proliferation.