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000124453 1001_ $$0P:(DE-He78)3860e24c3868c15255c3383a58e8d5b8$$aBrocks, David$$b0$$eFirst author
000124453 245__ $$aDNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats.
000124453 260__ $$aNew York, NY$$bNature America$$c2017
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000124453 520__ $$aSeveral mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions. TINAT transcription after DNMTi treatment coincided with DNA hypomethylation and gain of classical promoter histone marks, while HDACi specifically induced a subset of TINATs in association with H2AK9ac, H3K14ac, and H3K23ac. Despite this mechanistic difference, both inhibitors convergently induced transcription from identical sites, as we found TINATs to be encoded in solitary long terminal repeats of the ERV9/LTR12 family, which are epigenetically repressed in virtually all normal cells.
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000124453 7001_ $$0P:(DE-HGF)0$$aSchmidt, Christopher R$$b1
000124453 7001_ $$0P:(DE-He78)bb7dadf5553886cba21a0a822f1c7ab4$$aDaskalakis, Michael$$b2
000124453 7001_ $$aJang, Hyo Sik$$b3
000124453 7001_ $$aShah, Nakul M$$b4
000124453 7001_ $$aLi, Daofeng$$b5
000124453 7001_ $$aLi, Jing$$b6
000124453 7001_ $$aZhang, Bo$$b7
000124453 7001_ $$00000-0002-6086-6434$$aHou, Yiran$$b8
000124453 7001_ $$0P:(DE-He78)3ca4e0a81d07c5f9bf4a6fdbd176ebbb$$aLaudato, Sara$$b9
000124453 7001_ $$0P:(DE-He78)c403a040c97f91902a7d31b93859f9fc$$aLipka, Daniel$$b10
000124453 7001_ $$0P:(DE-He78)1bd20c9facf01a9dd3eae38ef6a7e137$$aSchott, Johanna$$b11
000124453 7001_ $$0P:(DE-He78)24e1875bcb82cad9041058a56df01070$$aBierhoff, Holger$$b12
000124453 7001_ $$0P:(DE-He78)45a6854ecf41ba2e65ca3ba0d560f14c$$aAssenov, Yassen$$b13
000124453 7001_ $$0P:(DE-He78)15f2edbdcac0dd9b5685c52e3c90499c$$aHelf, Monika$$b14
000124453 7001_ $$0P:(DE-He78)1ff863117efdebc97730d2cd926e77b9$$aRessnerova, Alzbeta$$b15
000124453 7001_ $$0P:(DE-He78)0ed5fa378f10730f7d79044e8c25b750$$aIslam, Md Saiful$$b16
000124453 7001_ $$0P:(DE-HGF)0$$aLindroth, Anders M$$b17
000124453 7001_ $$0P:(DE-He78)a5ec4e2fef99022a37a6b07c2fdd6325$$aHaas, Simon$$b18
000124453 7001_ $$0P:(DE-He78)ba3fae49054b6bfaaa289b05ecd936d6$$aEssers, Marieke$$b19
000124453 7001_ $$0P:(DE-HGF)0$$aImbusch, Charles D$$b20
000124453 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b21
000124453 7001_ $$0P:(DE-He78)908367a659dea9e28dac34592b3c46e5$$aOehme, Ina$$b22
000124453 7001_ $$0P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aWitt, Olaf$$b23
000124453 7001_ $$0P:(DE-HGF)0$$aLübbert, Michael$$b24
000124453 7001_ $$0P:(DE-He78)697cb039ca08f3b7e5a2a52dbf020b46$$aMallm, Jan-Philipp$$b25
000124453 7001_ $$00000-0001-9951-9395$$aRippe, Karsten$$b26
000124453 7001_ $$0P:(DE-He78)18218139eec55d83cf82679934e5cd75$$aWill, Rainer$$b27
000124453 7001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b28
000124453 7001_ $$00000-0001-9284-9834$$aStoecklin, Georg$$b29
000124453 7001_ $$0P:(DE-He78)3c4679d03b730156fae20c4948722efe$$aGerhäuser, Clarissa$$b30
000124453 7001_ $$0P:(DE-HGF)0$$aOakes, Christopher C$$b31
000124453 7001_ $$aWang, Ting$$b32
000124453 7001_ $$00000-0003-2554-3952$$aPlass, Christoph$$b33$$eLast author
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