Strategic Communication 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 institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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