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000130847 1001_ $$0P:(DE-He78)c566ec22a882273029b7cbe4ef700428$$aWeigel, Christoph$$b0$$eFirst author$$udkfz
000130847 245__ $$aEpigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.
000130847 260__ $$aLondon$$bNature Publishing Group$$c2016
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000130847 520__ $$aRadiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.
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000130847 650_7 $$2NLM Chemicals$$aEGR1 protein, human
000130847 650_7 $$2NLM Chemicals$$aEarly Growth Response Protein 1
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000130847 650_7 $$0EC 2.7.1.107$$2NLM Chemicals$$aDiacylglycerol Kinase
000130847 7001_ $$aVeldwijk, Marlon R$$b1
000130847 7001_ $$0P:(DE-HGF)0$$aOakes, Christopher C$$b2
000130847 7001_ $$0P:(DE-He78)fd17a8dbf8d08ea5bb656dfef7398215$$aSeibold, Petra$$b3$$udkfz
000130847 7001_ $$0P:(DE-He78)4169c43af2de6fae487c89fc2e7cfaa8$$aSlynko, Alla$$b4$$udkfz
000130847 7001_ $$0P:(DE-HGF)0$$aLiesenfeld, David B$$b5
000130847 7001_ $$0P:(DE-HGF)0$$aRabionet, Mariona$$b6
000130847 7001_ $$0P:(DE-He78)ebc7b75d75b6c73bafffa8b7882df2a0$$aHanke, Sabrina$$b7$$udkfz
000130847 7001_ $$aWenz, Frederik$$b8
000130847 7001_ $$aSperk, Elena$$b9
000130847 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b10$$udkfz
000130847 7001_ $$0P:(DE-He78)f185c4fb611183f9ec2258f7a5231bbc$$aRösli, Christoph$$b11$$udkfz
000130847 7001_ $$0P:(DE-He78)a928ded2085c8911822370cad0b4a728$$aSandhoff, Roger$$b12$$udkfz
000130847 7001_ $$0P:(DE-He78)45a6854ecf41ba2e65ca3ba0d560f14c$$aAssenov, Yassen$$b13$$udkfz
000130847 7001_ $$00000-0003-2554-3952$$aPlass, Christoph$$b14
000130847 7001_ $$aHerskind, Carsten$$b15
000130847 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b16$$udkfz
000130847 7001_ $$0P:(DE-He78)141ce740f5d881812d2675147b72ecaf$$aSchmezer, Peter$$b17$$udkfz
000130847 7001_ $$00000-0002-5594-5736$$aPopanda, Odilia$$b18$$eLast author
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