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Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A

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 lo...

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Hauptverfasser: Arab, Khelifa (VerfasserIn) , Park, Yoon Jung (VerfasserIn) , Lindroth, Anders M. (VerfasserIn) , Schäfer, Andrea (VerfasserIn) , Oakes, Christopher (VerfasserIn) , Weichenhan, Dieter (VerfasserIn) , Lukanova, Annekatrin (VerfasserIn) , Lundin, Eva (VerfasserIn) , Risch, Angela (VerfasserIn) , Meister, Michael (VerfasserIn) , Dienemann, Hendrik (VerfasserIn) , Dyckhoff, Gerhard (VerfasserIn) , Herold-Mende, Christel (VerfasserIn) , Grummt, Ingrid (VerfasserIn) , Niehrs, Christof (VerfasserIn) , Plass, Christoph (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 31, 2014
In: Molecular cell
Year: 2014, Jahrgang: 55, Heft: 4, Pages: 604-614
ISSN:1097-4164
DOI:10.1016/j.molcel.2014.06.031
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molcel.2014.06.031
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1097276514005656
Volltext
Verfasserangaben:Khelifa Arab, Yoon Jung Park, Anders M. Lindroth, Andrea Schäfer, Christopher Oakes, Dieter Weichenhan, Annekatrin Lukanova, Eva Lundin, Angela Risch, Michael Meister, Hendrik Dienemann, Gerhard Dyckhoff, Christel Herold-Mende, Ingrid Grummt, Christof Niehrs, and Christoph Plass
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 29.07.2020
Beschreibung:Online Resource
ISSN:1097-4164
DOI:10.1016/j.molcel.2014.06.031

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