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@ARTICLE{Yildiz:1019800,
author = {Yildiz, Can Bora and Kundu, Tathagata and Gehrmann, Julia
and Koesling, Jannis and Ravaei, Amin and Wolff, Philip and
Kraft, Florian and Maié, Tiago and Jakovcevski, Mira and
Pensold, Daniel and Zimmermann, Olav and Rossetti, Giulia
and Costa, Ivan G. and Zimmer-Bensch, Geraldine},
title = {{E}phrin{A}5 regulates cell motility by modulating
{S}nhg15/{DNA} triplex-dependent targeting of {DNMT}1 to the
{N}cam1 promoter},
journal = {Epigenetics $\&$ chromatin},
volume = {16},
number = {1},
issn = {1756-8935},
address = {London},
publisher = {BioMed Central},
reportid = {FZJ-2023-05631},
pages = {42},
year = {2023},
abstract = {Cell–cell communication is mediated by membrane receptors
and their ligands, such as the Eph/ephrin system,
orchestrating cell migration during development and in
diverse cancer types. Epigenetic mechanisms are key for
integrating external “signals”, e.g., from neighboring
cells, into the transcriptome in health and disease.
Previously, we reported ephrinA5 to trigger transcriptional
changes of lncRNAs and protein-coding genes in cerebellar
granule cells, a cell model for medulloblastoma. LncRNAs
represent important adaptors for epigenetic writers through
which they regulate gene expression. Here, we investigate a
lncRNA-mediated targeting of DNMT1 to specific gene loci by
the combined power of in silico modeling of RNA/DNA
interactions and wet lab approaches, in the context of the
clinically relevant use case of ephrinA5-dependent
regulation of cellular motility of cerebellar granule cells.
We provide evidence that Snhg15, a cancer-related lncRNA,
recruits DNMT1 to the Ncam1 promoter through RNA/DNA triplex
structure formation and the interaction with DNMT1. This
mediates DNA methylation-dependent silencing of Ncam1, being
abolished by ephrinA5 stimulation-triggered reduction of
Snhg15 expression. Hence, we here propose a triple helix
recognition mechanism, underlying cell motility regulation
via lncRNA-targeted DNA methylation in a clinically relevant
context.},
cin = {JSC / IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)IAS-5-20120330 /
I:(DE-Juel1)INM-9-20140121},
pnm = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
(SDLs) and Research Groups (POF4-511) / 5241 - Molecular
Information Processing in Cellular Systems (POF4-524) / GRK
2416 - GRK 2416: MultiSenses-MultiScales: Neue Ansätze zur
Aufklärung neuronaler multisensorischer Integration
(368482240) / OPSF678 - Establishing pipelines for machine
learning and molecular simulation-based prediction of
lncRNA-DNA-protein interactions (EXS-SF-OPSF678)},
pid = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-5241 /
G:(GEPRIS)368482240 / G:(DE-82)EXS-SF-OPSF678},
typ = {PUB:(DE-HGF)16},
pubmed = {37880732},
UT = {WOS:001091019900001},
doi = {10.1186/s13072-023-00516-4},
url = {https://juser.fz-juelich.de/record/1019800},
}