Press and Public Relations

How silent genes are activated

No. 39ce | 28/08/2014

© Christopf Bock Wikimedia commons

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. Scientists from the German Cancer Research Center, DKFZ, Heidelberg, including Ingrid Grummt, Christoph Niehrs and Christoph Plass, show in the latest issue of Molecular Cell that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates tumor suppressor gene 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. First author Khelifa Arab says: "The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes."

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: Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A. Molecular Cell 2014, DOI: 10.1016/j.molcel.2014.06.031

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

RSS-Feed

Subscribe to our RSS-Feed.

to top