Cooperation of LIM domain-binding 2 (LDB2) with EGR in the pathogenesis of schizophrenia.
ChIP-seq
amygdala
balanced chromosomal translocation
behavior
knockout mouse
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
09 04 2021
09 04 2021
Historique:
revised:
21
01
2021
received:
22
04
2020
accepted:
25
01
2021
pubmed:
4
3
2021
medline:
26
10
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
Genomic defects with large effect size can help elucidate unknown pathologic architecture of mental disorders. We previously reported on a patient with schizophrenia and a balanced translocation between chromosomes 4 and 13 and found that the breakpoint within chromosome 4 is located near the LDB2 gene. We show here that Ldb2 knockout (KO) mice displayed multiple deficits relevant to mental disorders. In particular, Ldb2 KO mice exhibited deficits in the fear-conditioning paradigm. Analysis of the amygdala suggested that dysregulation of synaptic activities controlled by the immediate early gene Arc is involved in the phenotypes. We show that LDB2 forms protein complexes with known transcription factors. Consistently, ChIP-seq analyses indicated that LDB2 binds to > 10,000 genomic sites in human neurospheres. We found that many of those sites, including the promoter region of ARC, are occupied by EGR transcription factors. Our previous study showed an association of the EGR family genes with schizophrenia. Collectively, the findings suggest that dysregulation in the gene expression controlled by the LDB2-EGR axis underlies a pathogenesis of subset of mental disorders.
Identifiants
pubmed: 33656268
doi: 10.15252/emmm.202012574
pmc: PMC8033514
doi:
Substances chimiques
LDB2 protein, human
0
LIM Domain Proteins
0
Ldb2 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12574Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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