Rabbit Anti-Human TET3 (a.a. 1561-1660) Polyclonal antibody

DNA methylation is one of the best-characterized epigenetic modifications(1-4). Although the enzymes that catalyse DNA methylation have been characterized, enzymes responsible for demethylation have been elusive(5). A recent study indicates that the human TET1 protein could catalyse the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), raising the possibility that DNA demethylation may be a Tet1-mediated process(6). Here we extend this study by demonstrating that all three mouse Tet proteins (Tet1, Tet2 and Tet3) can also catalyse a similar reaction. Tet1 has an important role in mouse embryonic stem (ES) cell maintenance through maintaining the expression of Nanog in ES cells. Downregulation of Nanog via Tet1 knockdown correlates with methylation of the Nanog promoter, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in pre-implantation embryos results in a bias towards trophectoderm differentiation. Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification.

Background; Accumulating evidence suggests that epigenetic changes play key roles in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the dynamic regulation of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in diabetic peripheral blood DNA remains to be elucidated. Results: We collected fasting blood samples (104 patients and 108 healthy controls) and glucose-stimulated blood samples at different time points (11 patients and 5 healthy controls underwent oral glucose tolerance test (OGTT)), as well as blood samples from six couples of diabetic and control rats. A HPLC-MS/MS system was used for quantifying global 5mC and 5hmC in genomic DNA from white blood cells (WBCs), and qPCR was performed for detecting mRNA expression of SIRT6 and TETs. We found that global 5mC decreased, while global 5hmC increased in both patients and diabetic rats, with lower 5mC being a risk factor of T2DM (OR = 0.524, 95%CI 0.402-0.683, p = 1.64 x 10(-6)). The OGTT data from patients showed that 5mC declined within 1h and then returned to the fasting status at 2h, while 5hmC rose from 0.5h to 3h with increasing glucose. However, the similar patterns were not found in the controls. The mRNA expression of TET2, TET3, and SIRT6 was upregulated in patients (p = 0.012, p = 0.026, and p = 0.035, respectively). The similar results were observed in diabetic OGTT and rats. Correlation analysis indicated that SIRT6 was positively correlated with TET2 in humans (r = 0.277, p < 0.001) and rats (r = 0.942, p < 0.001), in addition to a correlation between glucose and SIRT6 (r = 0.162, p = 0.045) and TET2 (r = 0.174, p = 0.036). Conclusions: Hyperglycemia appeared to promote the mRNA expression of SIRT6 and TETs, which in turn might cause the dynamic changes of 5mC and 5hmC in WBCs from T2DM patients.