| First Author | Wang S | Year | 2017 |
| Journal | FEBS Lett | Volume | 591 |
| Issue | 13 | Pages | 1929-1939 |
| PubMed ID | 28542810 | Mgi Jnum | J:244809 |
| Mgi Id | MGI:5913588 | Doi | 10.1002/1873-3468.12690 |
| Citation | Wang S, et al. (2017) DNMT1 cooperates with MBD4 to inhibit the expression of Glucocorticoid-induced TNFR-related protein in human T cells. FEBS Lett 591(13):1929-1939 |
| abstractText | Glucocorticoid-induced TNFR-related protein (GITR) is constitutively expressed in T regulatory (Treg) cells and regulates their suppressive function. We identified two methylated CpG islands in the Gitr locus. Using a ChIP assay, we demonstrate that both DNMT1 and methyl-CpG-binding domain Protein 4 (MBD4) bind to the Gitr promoter. Moreover, knockdown of DNMT1 decreases the binding activity of MBD4. We observed much higher levels of both DNMT1 and MBD4 in human CD4+ CD25- conventional T (Tconv) cells. Moreover, co-overexpression of DNMT1 and MBD4 in Treg cells significantly inhibits GITR expression and impairs their suppressive activity. Our results reveal a novel molecular mechanism by which MBD4 inhibits GITR expression in a DNMT1-dependent manner. |
