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@ARTICLE{Arasappan:889304,
author = {Arasappan, Dhivya and Eickhoff, Simon B. and Nemeroff,
Charles B. and Hofmann, Hans A. and Jabbi, Mbemba},
title = {{T}ranscription {F}actor {M}otifs {A}ssociated with
{A}nterior {I}nsula {G}ene {E}xpression {U}nderlying {M}ood
{D}isorder {P}henotypes},
journal = {Molecular neurobiology},
volume = {58},
issn = {1559-1182},
address = {Totowa, NJ},
publisher = {Humana Press},
reportid = {FZJ-2021-00196},
pages = {1978–1989},
year = {2021},
note = {This work was supported by the Dell Medical School, UT
Austin Mulva Neuroscience Clinics Startup funds for MJ; DA
and CBN are supported by the National Institutes of Health
(NIH) and HH is supported by NSF.The funding bodies nor any
other entities were involved in the design of the study and
collection, analysis, and interpretation of data presented
here.},
abstract = {Mood disorders represent a major cause of morbidity and
mortality worldwide but the brain-related molecular
pathophysiology in mood disorders remains largely undefined.
Because the anterior insula is reduced in volume in patients
with mood disorders, RNA was extracted from the anterior
insula postmortem anterior insula of mood disorder samples
and compared with unaffected controls 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. 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. Robust imaging-guided transcriptomics by using
meta-analytic imaging results to guide independent
postmortem 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. Our findings of
TF-motifs that regulate the expression of immune, cellular
homeostatic-control, and developmental genes provide novel
information about the hierarchical 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 = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {33411239},
UT = {WOS:000605898700001},
doi = {10.1007/s12035-020-02195-8},
url = {https://juser.fz-juelich.de/record/889304},
}