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@ARTICLE{Weber:140109,
author = {Weber, Axel and Schwarz, Sigrid C and Tost, Jörg and
Trümbach, Dietrich and Winter, Pia and Busato, Florence and
Tacik, Pawel and Windhorst, Anita C and Fagny, Maud and
Arzberger, Thomas and McLean, Catriona and van Swieten, John
C and Schwarz, Johannes and Vogt-Weisenhorn, Daniela and
Wurst, Wolfgang and Adhikary, Till and Dickson, Dennis W and
Höglinger, Günter U and Müller, Ulrich},
title = {{E}pigenome-wide {DNA} methylation profiling in
{P}rogressive {S}upranuclear {P}alsy reveals major changes
at {DLX}1.},
journal = {Nature Communications},
volume = {9},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2020-06431},
pages = {2929},
year = {2018},
abstract = {Genetic, epigenetic, and environmental factors contribute
to the multifactorial disorder progressive supranuclear
palsy (PSP). Here, we study epigenetic changes by
genome-wide analysis of DNA from postmortem tissue of
forebrains of patients and controls and detect significant
(P < 0.05) methylation differences at 717 CpG sites in
PSP vs. controls. Four-hundred fifty-one of these sites are
associated with protein-coding genes. While differential
methylation only affects a few sites in most genes, DLX1 is
hypermethylated at multiple sites. Expression of an
antisense transcript of DLX1, DLX1AS, is reduced in PSP
brains. The amount of DLX1 protein is increased in gray
matter of PSP forebrains. Pathway analysis suggests that
DLX1 influences MAPT-encoded Tau protein. In a cell system,
overexpression of DLX1 results in downregulation of MAPT
while overexpression of DLX1AS causes upregulation of MAPT.
Our observations suggest that altered DLX1 methylation and
expression contribute to pathogenesis of PSP by influencing
MAPT.},
keywords = {Aged / Aged, 80 and over / DNA Methylation: genetics /
Epigenesis, Genetic: genetics / Female / Homeodomain
Proteins: genetics / Homeodomain Proteins: metabolism /
Humans / Male / Supranuclear Palsy, Progressive: genetics /
Supranuclear Palsy, Progressive: pathology / Transcription
Factors: genetics / Transcription Factors: metabolism / tau
Proteins: genetics / tau Proteins: metabolism / Distal-less
homeobox proteins (NLM Chemicals) / Homeodomain Proteins
(NLM Chemicals) / MAPT protein, human (NLM Chemicals) /
Transcription Factors (NLM Chemicals) / tau Proteins (NLM
Chemicals)},
cin = {AG Höglinger 1 / AG Levin / Ext HZM / AG Wurst},
ddc = {500},
cid = {I:(DE-2719)1110002 / I:(DE-2719)1111016 /
I:(DE-2719)5000050 / I:(DE-2719)1140001},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
- Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30050033},
pmc = {pmc:PMC6062504},
doi = {10.1038/s41467-018-05325-y},
url = {https://pub.dzne.de/record/140109},
}