TY  - JOUR
AU  - Brocks, David
AU  - Schmidt, Christopher R
AU  - Daskalakis, Michael
AU  - Jang, Hyo Sik
AU  - Shah, Nakul M
AU  - Li, Daofeng
AU  - Li, Jing
AU  - Zhang, Bo
AU  - Hou, Yiran
AU  - Laudato, Sara
AU  - Lipka, Daniel
AU  - Schott, Johanna
AU  - Bierhoff, Holger
AU  - Assenov, Yassen
AU  - Helf, Monika
AU  - Ressnerova, Alzbeta
AU  - Islam, Md Saiful
AU  - Lindroth, Anders M
AU  - Haas, Simon
AU  - Essers, Marieke
AU  - Imbusch, Charles D
AU  - Brors, Benedikt
AU  - Oehme, Ina
AU  - Witt, Olaf
AU  - Lübbert, Michael
AU  - Mallm, Jan-Philipp
AU  - Rippe, Karsten
AU  - Will, Rainer
AU  - Weichenhan, Dieter
AU  - Stoecklin, Georg
AU  - Gerhäuser, Clarissa
AU  - Oakes, Christopher C
AU  - Wang, Ting
AU  - Plass, Christoph
TI  - DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats.
JO  - Nature genetics
VL  - 49
IS  - 7
SN  - 1546-1718
CY  - New York, NY
PB  - Nature America
M1  - DKFZ-2017-01330
SP  - 1052 - 1060
PY  - 2017
AB  - Several 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28604729
DO  - DOI:10.1038/ng.3889
UR  - https://inrepo02.dkfz.de/record/124453
ER  -