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@ARTICLE{Ecker:157624,
author = {J. Ecker$^*$ and V. Thatikonda$^*$ and G. Sigismondo$^*$
and F. Selt$^*$ and G. Valinciute$^*$ and I. Oehme$^*$ and
C. Müller$^*$ and J. L. Buhl$^*$ and J. Ridinger$^*$ and D.
Usta$^*$ and N. Qin$^*$ and C. M. van Tilburg$^*$ and C.
Herold-Mende and M. Remke$^*$ and F. Sahm$^*$ and F.
Westermann$^*$ and M. Kool$^*$ and R. J. Wechsler-Reya and
L. Chavez and J. Krijgsveld$^*$ and N. Jäger$^*$ and S. M.
Pfister$^*$ and O. Witt$^*$ and T. Milde$^*$},
title = {{R}educed chromatin binding of {MYC} is a key effect of
{HDAC} inhibition in {MYC} amplified medulloblastoma.},
journal = {Neuro-Oncology},
volume = {23},
number = {2},
issn = {1523-5866},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2020-01721},
pages = {226-239},
year = {2021},
note = {#EA:B310#LA:B310#2021 Feb 25;23(2):226-239},
abstract = {The sensitivity of MYC amplified medulloblastoma to class I
HDAC inhibition has been shown previously, however
understanding the underlying molecular mechanism is crucial
for selection of effective HDAC inhibitors for clinical use.
The aim of this study was to investigate the direct
molecular interaction of MYC and the class I HDAC2, and the
impact of class I HDAC inhibition on MYC
function.Co-immunoprecipitation and mass spectrometry was
used to determine the co-localization of MYC and HDAC2.
ChIP-sequencing and gene expression profiling was used to
analyze the co- localization of MYC and HDAC2 on DNA and the
impact on transcriptional activity in primary tumors and a
MYC amplified cell line treated with the class I HDAC
inhibitor entinostat. The effect on MYC was investigated by
quantitative RT-PCR, Western blot and
immunofluorescence.HDAC2 is a cofactor of MYC in MYC
amplified medulloblastoma. The MYC-HDAC2 complex is bound to
genes defining the MYC-dependent transcriptional profile.
Class I HDAC inhibition leads to stabilization and reduced
DNA-binding of MYC protein inducing a down-regulation of MYC
activated genes (MAGs) and up-regulation of MYC repressed
genes (MRGs). MAGs and MRGs are characterized by opposing
biological functions and by distinct E-box distribution.Our
data elucidates the molecular interaction of MYC and HDAC2
and support a model in which inhibition of class I HDACs
directly targets MYC´s trans-activating and
trans-repressing function.},
cin = {B310 / HD01 / B062 / ED01 / B300 / B087 / B230},
ddc = {610},
cid = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)ED01-20160331 /
I:(DE-He78)B300-20160331 / I:(DE-He78)B087-20160331 /
I:(DE-He78)B230-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32822486},
doi = {10.1093/neuonc/noaa191},
url = {https://inrepo02.dkfz.de/record/157624},
}