DNA甲基化是一种表观遗传修饰，调控基因表达，在造血过程中起着重要作用。UHRF1和DNMT1 在调控DNA甲基化在整个基因组范围内的维持中都至关重要。明确的是，高度甲基化是急性髓系白血病（AML）的重要特征。然而，DNA甲基化如何调控包括THP-1在内的AML细胞的分化机制尚不完全清楚。本研究报道了UHRF1或DNMT1耗竭增强了THP-1细胞对PMA诱导的分化。转录组分析和基因组甲基化阵列结果表明，UHRF1或DNMT1 耗竭导致THP-1细胞对PMA产生了高度敏感性的变化。此外，UHRF1或DNMT1的减少阻碍了异种移植小鼠模型中固肿瘤的形成。这些发现表明，UHRF1和DNMT1在调控THP-1细胞的分化和增殖中发挥着关键作用，靶向这些蛋白可能提高AML患者的分化治疗效果。© 2023年。Springer Nature有限公司。

DNA methylation is an epigenetic modification that regulates gene expression and plays an essential role in hematopoiesis. UHRF1 and DNMT1 are both crucial for regulating genome-wide maintenance of DNA methylation. Specifically, it is well known that hypermethylation is crucial characteristic of acute myeloid leukemia (AML). However, the mechanism underlying how DNA methylation regulates the differentiation of AML cells, including THP-1 is not fully elucidated. In this study, we report that UHRF1 or DNMT1 depletion enhances the phorbol-12-myristate-13-acetate (PMA)-induced differentiation of THP-1 cells. Transcriptome analysis and genome-wide methylation array results showed that depleting UHRF1 or DNMT1 induced changes that made THP-1 cells highly sensitive to PMA. Furthermore, knockdown of UHRF1 or DNMT1 impeded solid tumor formation in xenograft mouse model. These findings suggest that UHRF1 and DNMT1 play a pivotal role in regulating differentiation and proliferation of THP-1 cells and targeting these proteins may improve the efficiency of differentiation therapy in AML patients.© 2023. Springer Nature Limited.