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@ARTICLE{Arasappan:889988,
author = {Arasappan, Dhivya and Eickhoff, Simon B. and Nemeroff,
Charles B and Hofmann, Hans A. and Jabbi, Mbemba},
title = {{T}ranscription factor motifs associated with anterior
insula gene-expression underlying mood disorder phenotypes},
journal = {Molecular neurobiology},
issn = {0893-7648},
address = {Totowa, NJ},
publisher = {Humana Press},
reportid = {FZJ-2021-00583},
year = {2019},
abstract = {Background: Mood disorders represent a major cause of
morbidity and mortality worldwide but the brain-related
molecular pathophysiology in mood disorders remains largely
undefined. Methods: Because the anterior insula is reduced
in volume in patients with mood disorders, RNA was extracted
from postmortem mood disorder samples and compared with
unaffected control samples for RNA-sequencing identification
of differentially expressed genes (DEGs) in a) bipolar
disorder (BD; n=37) versus (vs.) controls (n=33), and b)
major depressive disorder (MDD n=30) vs controls, and c) low
vs. high Axis-I comorbidity (a measure of cumulative
psychiatric disease burden). Given the regulatory role of
transcription factors (TFs) in gene expression via
specific-DNA-binding domains (motifs), we used JASPAR TF
binding database to identify TF-motifs. Results: We found
that DEGs in BD vs. controls, MDD vs. controls, and high vs.
low Axis-I comorbidity were associated with TF-motifs that
are known to regulate expression of toll-like receptor
genes, cellular homeostatic-control genes, and genes
involved in embryonic, cellular/organ and brain development.
Discussion: Robust imaging-guided transcriptomics (i.e.,
using meta-analytic imaging results to guide independent
post-mortem dissection for RNA-sequencing) was applied by
targeting the gray matter volume reduction in the anterior
insula in mood disorders, to guide independent postmortem
identification of TF motifs regulating DEG. TF motifs were
identified for immune, cellular, embryonic and
neurodevelopmental processes. Conclusion: Our findings of
TF-motifs that regulate the expression of immune, cellular
homeostatic-control, and developmental genes provides novel
information about the hierarchical .CC-BY-NC-ND 4.0
International licenseunder anot certified by peer review) is
the author/funder, who has granted bioRxiv a license to
display the preprint in perpetuity. It is made available The
copyright holder for this preprint (which wasthis version
posted September 28, 2020. ;
https://doi.org/10.1101/864900doi: bioRxiv preprint 3
relationship between gene regulatory networks, the TFs that
control them, and proximate underlying neuroanatomical
phenotypes in mood disorders.},
cin = {INM-7},
ddc = {570},
cid = {I:(DE-Juel1)INM-7-20090406},
pnm = {572 - (Dys-)function and Plasticity (POF3-572)},
pid = {G:(DE-HGF)POF3-572},
typ = {PUB:(DE-HGF)25},
doi = {10.1101/864900},
url = {https://juser.fz-juelich.de/record/889988},
}