% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Ottema:176967,
author = {S. Ottema and R. Mulet-Lazaro and C. Erpelinck-Verschueren
and S. van Herk and M. Havermans and A. Arricibita Varea and
M. Vermeulen and H. B. Beverloo and S. Gröschel$^*$ and T.
Haferlach and C. Haferlach and B. J Wouters and E. Bindels
and L. Smeenk and R. Delwel},
title = {{T}he leukemic oncogene {EVI}1 hijacks a {MYC}
super-enhancer by {CTCF}-facilitated loops.},
journal = {Nature Communications},
volume = {12},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2021-02200},
pages = {5679},
year = {2021},
abstract = {Chromosomal rearrangements are a frequent cause of oncogene
deregulation in human malignancies. Overexpression of EVI1
is found in a subgroup of acute myeloid leukemia (AML) with
3q26 chromosomal rearrangements, which is often therapy
resistant. In AMLs harboring a t(3;8)(q26;q24), we observed
the translocation of a MYC super-enhancer (MYC SE) to the
EVI1 locus. We generated an in vitro model mimicking a
patient-based t(3;8)(q26;q24) using CRISPR-Cas9 technology
and demonstrated hyperactivation of EVI1 by the hijacked MYC
SE. This MYC SE contains multiple enhancer modules, of which
only one recruits transcription factors active in early
hematopoiesis. This enhancer module is critical for EVI1
overexpression as well as enhancer-promoter interaction.
Multiple CTCF binding regions in the MYC SE facilitate this
enhancer-promoter interaction, which also involves a CTCF
binding site upstream of the EVI1 promoter. We hypothesize
that this CTCF site acts as an enhancer-docking site in
t(3;8) AML. Genomic analyses of other 3q26-rearranged AML
patient cells point to a common mechanism by which EVI1 uses
this docking site to hijack enhancers active in early
hematopoiesis.},
cin = {A380},
ddc = {500},
cid = {I:(DE-He78)A380-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34584081},
doi = {10.1038/s41467-021-25862-3},
url = {https://inrepo02.dkfz.de/record/176967},
}