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@ARTICLE{Brocks:124453,
author = {D. Brocks$^*$ and C. R. Schmidt$^*$ and M. Daskalakis$^*$
and H. S. Jang and N. M. Shah and D. Li and J. Li and B.
Zhang and Y. Hou and S. Laudato$^*$ and D. Lipka$^*$ and J.
Schott$^*$ and H. Bierhoff$^*$ and Y. Assenov$^*$ and M.
Helf$^*$ and A. Ressnerova$^*$ and M. S. Islam$^*$ and A. M.
Lindroth$^*$ and S. Haas$^*$ and M. Essers$^*$ and C. D.
Imbusch$^*$ and B. Brors$^*$ and I. Oehme$^*$ and O.
Witt$^*$ and M. Lübbert$^*$ and J.-P. Mallm$^*$ and K.
Rippe$^*$ and R. Will$^*$ and D. Weichenhan$^*$ and G.
Stoecklin and C. Gerhäuser$^*$ and C. C. Oakes$^*$ and T.
Wang and C. Plass$^*$},
title = {{DNMT} and {HDAC} inhibitors induce cryptic transcription
start sites encoded in long terminal repeats.},
journal = {Nature genetics},
volume = {49},
number = {7},
issn = {1546-1718},
address = {New York, NY},
publisher = {Nature America},
reportid = {DKFZ-2017-01330},
pages = {1052 - 1060},
year = {2017},
abstract = {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.},
cin = {C010 / V960 / G200 / G340 / B066 / A200 / A030 / L101 /
L601},
ddc = {570},
cid = {I:(DE-He78)C010-20160331 / I:(DE-He78)V960-20160331 /
I:(DE-He78)G200-20160331 / I:(DE-He78)G340-20160331 /
I:(DE-He78)B066-20160331 / I:(DE-He78)A200-20160331 /
I:(DE-He78)A030-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)L601-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28604729},
doi = {10.1038/ng.3889},
url = {https://inrepo02.dkfz.de/record/124453},
}