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| Home > Publications database > Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis. > print |
| 001 | 130847 | ||
| 005 | 20240228143501.0 | ||
| 024 | 7 | _ | |a 10.1038/ncomms10893 |2 doi |
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| 037 | _ | _ | |a DKFZ-2017-05925 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Weigel, Christoph |0 P:(DE-He78)c566ec22a882273029b7cbe4ef700428 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis. |
| 260 | _ | _ | |a London |c 2016 |b Nature Publishing Group |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1522240704_30780 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Radiotherapy 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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| 650 | _ | 7 | |a EGR1 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Early Growth Response Protein 1 |2 NLM Chemicals |
| 650 | _ | 7 | |a RNA, Messenger |2 NLM Chemicals |
| 650 | _ | 7 | |a Diacylglycerol Kinase |0 EC 2.7.1.107 |2 NLM Chemicals |
| 700 | 1 | _ | |a Veldwijk, Marlon R |b 1 |
| 700 | 1 | _ | |a Oakes, Christopher C |0 P:(DE-HGF)0 |b 2 |
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| 700 | 1 | _ | |a Wenz, Frederik |b 8 |
| 700 | 1 | _ | |a Sperk, Elena |b 9 |
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| 700 | 1 | _ | |a Plass, Christoph |0 0000-0003-2554-3952 |b 14 |
| 700 | 1 | _ | |a Herskind, Carsten |b 15 |
| 700 | 1 | _ | |a Chang-Claude, Jenny |0 P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253 |b 16 |u dkfz |
| 700 | 1 | _ | |a Schmezer, Peter |0 P:(DE-He78)141ce740f5d881812d2675147b72ecaf |b 17 |u dkfz |
| 700 | 1 | _ | |a Popanda, Odilia |0 0000-0002-5594-5736 |b 18 |e Last author |
| 773 | _ | _ | |a 10.1038/ncomms10893 |g Vol. 7, p. 10893 - |0 PERI:(DE-600)2553671-0 |n NN |p 10893 - |t Nature Communications |v 7 |y 2016 |x 2041-1723 |
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