DNMT1 cooperates with MBD4 to inhibit the expression of Glucocorticoid-induced TNFR-related protein in human T cells.

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Wang S,Li Y,Zhu F,Lin F,Luo X,Zhao B,Zhang P,Li D,Gao Y,Liang R,Liu L,Tsun A,Yuan X,Wu K,Li B

doi

10.1002/1873-3468.12690

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

1929-1939

issue

13

eissn

0014-5793

issn

1873-3468

journal_volume

591

pub_type

信件
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