Identification of activity-induced Egr3-dependent genes reveals genes associated with DNA damage response and schizophrenia
Abstract Bioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder t...
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Published in | Translational psychiatry Vol. 12; no. 1; p. 320 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group
08.08.2022
Nature Publishing Group UK |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
Bioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder to Alzheimer’s disease. However, few studies have identified and validated
Egr3
-dependent genes in the mammalian brain. We have previously shown that
Egr3
is required for stress-responsive behavior, memory, and hippocampal long-term depression in mice. To identify
Egr3
-dependent genes that may regulate these processes, we conducted an expression microarray on hippocampi from wildtype (WT) and
Egr3−/−
mice following electroconvulsive seizure (ECS), a stimulus that induces maximal expression of immediate early genes including
Egr3
. We identified 69 genes that were differentially expressed between WT and
Egr3−/−
mice one hour following ECS. Bioinformatic analyses showed that many of these are altered in, or associated with, schizophrenia, including
Mef2c
and
Calb2
. Enrichr pathway analysis revealed the GADD45 (growth arrest and DNA-damage-inducible) family (
Gadd45b
,
Gadd45g
) as a leading group of differentially expressed genes. Together with differentially expressed genes in the AP-1 transcription factor family genes (
Fos
,
Fosb
), and the centromere organization protein
Cenpa
, these results revealed that
Egr3
is required for activity-dependent expression of genes involved in the DNA damage response. Our findings show that
EGR3
is critical for the expression of genes that are mis-expressed in schizophrenia and reveal a novel requirement for EGR3 in the expression of genes involved in activity-induced DNA damage response. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2158-3188 2158-3188 |
DOI: | 10.1038/s41398-022-02069-8 |