DNMT1 cooperates with MBD4 to inhibit the expression of Glucocorticoid‐induced TNFR‐related protein in human T cells. Issue 13 (10th June 2017)

• Record Type: Journal Article
• Authors: Wang, Shuaiwei; Li, Yangyang; Zhu, Fangming; Lin, Fang; Luo, Xuerui; Zhao, Binbin; Zhang, Peng; Li, Dan; Gao, Yayi; Liang, Rui; Liu, Luyan; Tsun, Andy; Yuan, Xiaojun; Wu, Kejin; Li, Bin
• Is Part Of: FEBS letters. Volume 591:Issue 13(2017)
• Page Start: 1929
• Page End: 1939
• Publication Date: 2017-06-10
• Subjects: DNA methylation -- DNMT1 -- GITR -- MBD4 -- Treg cells; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12690
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract :