Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A

被引：259

作者：

Arab, Khelifa ^{[1
,2
]}

Park, Yoon Jung ^{[2
]}

Lindroth, Anders M. ^{[2
]}

Schaefer, Andrea ^{[1
]}

Oakes, Christopher ^{[2
]}

Weichenhan, Dieter ^{[2
]}

Lukanova, Annekatrin ^{[3
,4
]}

Lundin, Eva ^{[4
]}

Risch, Angela ^{[2
,5
]}

Meister, Michael ^{[5
,6
]}

Dienemann, Hendrik ^{[5
,7
]}

Dyckhoff, Gerhard ^{[8
]}

Herold-Mende, Christel ^{[8
,9
]}

Grummt, Ingrid ^{[10
]}

Niehrs, Christof ^{[1
,11
]}

Plass, Christoph ^{[2
,12
]}

机构：

[1] IMB, D-55128 Mainz, Germany

[2] German Canc Res Ctr, Div Epigen & Canc Risk Factors, D-69120 Heidelberg, Germany

[3] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[4] Umea Univ, Dept Pathol, S-90185 Umea, Sweden

[5] Translat Lung Res Ctr Heidelberg TLRC, D-69120 Heidelberg, Germany

[6] Heidelberg Univ, Thoraxklin Heidelberg GGmbH, Translat Res Unit, D-69120 Heidelberg, Germany

[7] Heidelberg Univ, Thoraxklin Heidelberg GGmbH, Dept Thorac Surg, D-69120 Heidelberg, Germany

[8] Heidelberg Univ, Dept Otorhinolaryngol Head & Neck Surg, D-69120 Heidelberg, Germany

[9] Heidelberg Univ, Div Neurosurg Res, Dept Neurosurg, D-69120 Heidelberg, Germany

[10] DKFZ ZMBH Alliance, Div Mol Biol Cell 2, D-69120 Heidelberg, Germany

[11] DKFZ ZMBH Alliance, Div Mol Embryol, D-69120 Heidelberg, Germany

[12] German Canc Consortium, D-69120 Heidelberg, Germany

来源：

MOLECULAR CELL | 2014年 / 55卷 / 04期

基金：

欧洲研究理事会; 新加坡国家研究基金会; 美国国家卫生研究院;

关键词：

ACTIVE DNA DEMETHYLATION; EXCISION-REPAIR; MAMMALIAN DNA; TET PROTEINS; METHYLATION; PROMOTER; GLYCOSYLASE; LUNG; 5-HYDROXYMETHYLCYTOSINE; 5-METHYLCYTOSINE;

D O I：

10.1016/j.molcel.2014.06.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.

引用

页码：604 / 614

页数：11

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