中文摘要：

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。

英文摘要：

Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential role. To explore the function of Dnmt1, its expression was first profiled during the course of adipocyte differentiation of 3T3-L1 cells. The results revealed a dynamic regulation of its expression at the initiation stage. Knockdown of Dnmt1 compromised the differentiation process and decreased lipid production within the cells. To the aspect of epigenetic regulation, promoter methylation of Cdkn1a was significantly increased at the initiation stage of the differentiation, accompanied by decreased Cdkn1a expression. Furthermore, knockdown of Dnmt1 led to an increased Cdkn1a expression, indicating that Dnmt1 inhibits Cdkn1a expression by promoter methylation. Furthermore, we found that knockdown of Cdkn1a up-regulated the expression of PPARγ and resulted in enhanced adipocyte differentiation. In summary, our results demonstrated that Dnmt1 regulated the process of adipogenesis by methylation of Cdkn1a promoter, suggesting that Cdkn1a played a fundamental role in the prevention of adipocyte hyperplasia.