甲基化
表观遗传学
细胞生物学
癌症研究
抄写(语言学)
转录因子
染色质
脱甲基酶
癌变
转录调控
长非编码RNA
基因沉默
细胞周期
作者
Khelifa Arab,Yoon Jung Park,Anders Lindroth,Andrea I. Schäfer,Christopher C. Oakes,Dieter Weichenhan,Annekatrin Lukanova,Eva Lundin,Angela Risch,Michael Meister,Hendrik Dienemann,Gerhard Dyckhoff,Christel Herold-Mende,Ingrid Grummt,Christof Niehrs,Christoph Plass
出处
期刊:Molecular Cell
[Elsevier]
日期:2014-08-21
卷期号:55 (4): 604-614
被引量:188
标识
DOI:10.1016/j.molcel.2014.06.031
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.
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