DNA methylation alters the expression of certain genes without any alteration to the DNA sequence and is a dynamic process during normal hematopoietic differentiation. As an epigenetic regulator, methyl-CpG-binding domain protein 2 (MBD2) is an important member of the MBD protein family and is acknowledged as a “reader” of DNA methylation. We used a mouse model to study the effects of MBD2 on the early development of T cells. Here, we found that MBD2 deficiency led to retardation of T cell differentiation at the DN3 stage. Meanwhile, decreased proliferative capacity and increased apoptosis were detected in Mbd2^−/− DN thymocytes. Furthermore, we found the WNT pathway was significantly down-regulated in Mbd2^−/− DN thymocytes: DKK1 (Dickkopf-1) expression was significantly increased, while TCF7 (transcription factor 7) and c-MYC were down-regulated. Thus, these findings established that MBD2 acted as a dominant regulator to imprint DN T cell development via the WNT pathway.

DNA甲基化可改变某些基因的表达，而不会改变DNA序列，并且是正常造血分化过程中的一个动态过程。作为表观遗传调控因子，甲基CpG结合域蛋白2（MBD2）是MBD蛋白家族的重要成员，被公认为DNA甲基化的“阅读者”。我们使用小鼠模型研究了MBD2对T细胞早期发育的影响。在这里，我们发现MBD2缺乏症导致DN3期的T细胞分化受阻。同时，在Mbd2 ^-/- DN胸腺细胞中检测到增殖能力下降和凋亡增加。此外，我们发现WNT途径在Mbd2 ^-/-中显着下调DN胸腺细胞：DKK1（Dickkopf-1）表达显着增加，而TCF7（转录因子7）和c-MYC被下调。因此，这些发现确定MBD2充当主要调节剂，通过WNT途径印迹DN T细胞发育。