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@ARTICLE{Lin:129056,
author = {C. Y. Lin and S. Erkek$^*$ and Y. Tong$^*$ and L. Yin and
A. J. Federation and M. Zapatka$^*$ and P. Haldipur and D.
Kawauchi$^*$ and T. Risch and H.-J. Warnatz and B. Worst$^*$
and B. Ju and B. A. Orr and R. Zeid and D. R. Polaski and M.
Segura-Wang and S. M. Waszak and D. Jones$^*$ and M.
Kool$^*$ and V. Hovestadt$^*$ and I. Buchhalter$^*$ and L.
Sieber$^*$ and P. Johann$^*$ and L. Chavez$^*$ and S.
Gröschel$^*$ and M. Ryzhova and A. Korshunov$^*$ and W.
Chen and V. V. Chizhikov and K. J. Millen and V.
Amstislavskiy and H. Lehrach and M.-L. Yaspo and R. Eils$^*$
and P. Lichter$^*$ and J. O. Korbel and S. Pfister$^*$ and
J. E. Bradner and P. A. Northcott$^*$},
title = {{A}ctive medulloblastoma enhancers reveal subgroup-specific
cellular origins.},
journal = {Nature},
volume = {530},
number = {7588},
issn = {1476-4687},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2017-05061},
pages = {57 - 62},
year = {2016},
abstract = {Medulloblastoma is a highly malignant paediatric brain
tumour, often inflicting devastating consequences on the
developing child. Genomic studies have revealed four
distinct molecular subgroups with divergent biology and
clinical behaviour. An understanding of the regulatory
circuitry governing the transcriptional landscapes of
medulloblastoma subgroups, and how this relates to their
respective developmental origins, is lacking. Here, using
H3K27ac and BRD4 chromatin immunoprecipitation followed by
sequencing (ChIP-seq) coupled with tissue-matched DNA
methylation and transcriptome data, we describe the active
cis-regulatory landscape across 28 primary medulloblastoma
specimens. Analysis of differentially regulated enhancers
and super-enhancers reinforced inter-subgroup heterogeneity
and revealed novel, clinically relevant insights into
medulloblastoma biology. Computational reconstruction of
core regulatory circuitry identified a master set of
transcription factors, validated by ChIP-seq, that is
responsible for subgroup divergence, and implicates
candidate cells of origin for Group 4. Our integrated
analysis of enhancer elements in a large series of primary
tumour samples reveals insights into cis-regulatory
architecture, unrecognized dependencies, and cellular
origins.},
keywords = {Transcription Factors (NLM Chemicals)},
cin = {B062 / B060 / L101 / B080 / G100 / G240 / G380},
ddc = {070},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)L101-20160331 / I:(DE-He78)B080-20160331 /
I:(DE-He78)G100-20160331 / I:(DE-He78)G240-20160331 /
I:(DE-He78)G380-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26814967},
pmc = {pmc:PMC5168934},
doi = {10.1038/nature16546},
url = {https://inrepo02.dkfz.de/record/129056},
}