Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3

Persistent Link:
http://hdl.handle.net/10150/616973
Title:
Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3
Author:
Pfaffenseller, B; da Silva Magalhães, P V; De Bastiani, M A; Castro, M A A; Gallitano, A L; Kapczinski, F; Klamt, F
Affiliation:
Univ Arizona, Coll Med, Dept Basic Med Sci
Issue Date:
2016-05-10
Publisher:
NATURE PUBLISHING GROUP
Citation:
Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3 2016, 6 (5):e805 Translational Psychiatry
Journal:
Translational Psychiatry
Rights:
This work is licensed under a Creative Commons Attribution 4.0 International License.
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
Bipolar disorder (BD) is a severe mental illness with a strong genetic component. Despite its high degree of heritability, current genetic studies have failed to reveal individual loci of large effect size. In lieu of focusing on individual genes, we investigated regulatory units (regulons) in BD to identify candidate transcription factors (TFs) that regulate large groups of differentially expressed genes. Network-based approaches should elucidate the molecular pathways governing the pathophysiology of BD and reveal targets for potential therapeutic intervention. The data from a large-scale microarray study was used to reconstruct the transcriptional associations in the human prefrontal cortex, and results from two independent microarray data sets to obtain BD gene signatures. The regulatory network was derived by mapping the significant interactions between known TFs and all potential targets. Five regulons were identified in both transcriptional network models: early growth response 3 (EGR3), TSC22 domain family, member 4 (TSC22D4), interleukin enhancer-binding factor 2 (ILF2), Y-box binding protein 1 (YBX1) and MAP-kinase-activating death domain (MADD). With a high stringency threshold, the consensus across tests was achieved only for the EGR3 regulon. We identified EGR3 in the prefrontal cortex as a potential key target, robustly repressed in both BD signatures. Considering that EGR3 translates environmental stimuli into long-term changes in the brain, disruption in biological pathways involving EGR3 may induce an impaired response to stress and influence on risk for psychiatric disorders, particularly BD.
ISSN:
2158-3188
DOI:
10.1038/tp.2016.78
Version:
Final published version
Sponsors:
Brazilian fund CNPq/MS/SCTIE/DECIT-Pesquisas Sobre Doencas Neurodegenerativas [466989/2014-8]; Brazilian fund MCT/CNPq INCT-TM [573671/2008-7]; CAPES, Brazil; CNPq, Brazil
Additional Links:
http://www.nature.com/doifinder/10.1038/tp.2016.78

Full metadata record

DC FieldValue Language
dc.contributor.authorPfaffenseller, Ben
dc.contributor.authorda Silva Magalhães, P Ven
dc.contributor.authorDe Bastiani, M Aen
dc.contributor.authorCastro, M A Aen
dc.contributor.authorGallitano, A Len
dc.contributor.authorKapczinski, Fen
dc.contributor.authorKlamt, Fen
dc.date.accessioned2016-07-15T00:20:31Z-
dc.date.available2016-07-15T00:20:31Z-
dc.date.issued2016-05-10-
dc.identifier.citationDifferential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3 2016, 6 (5):e805 Translational Psychiatryen
dc.identifier.issn2158-3188-
dc.identifier.doi10.1038/tp.2016.78-
dc.identifier.urihttp://hdl.handle.net/10150/616973-
dc.description.abstractBipolar disorder (BD) is a severe mental illness with a strong genetic component. Despite its high degree of heritability, current genetic studies have failed to reveal individual loci of large effect size. In lieu of focusing on individual genes, we investigated regulatory units (regulons) in BD to identify candidate transcription factors (TFs) that regulate large groups of differentially expressed genes. Network-based approaches should elucidate the molecular pathways governing the pathophysiology of BD and reveal targets for potential therapeutic intervention. The data from a large-scale microarray study was used to reconstruct the transcriptional associations in the human prefrontal cortex, and results from two independent microarray data sets to obtain BD gene signatures. The regulatory network was derived by mapping the significant interactions between known TFs and all potential targets. Five regulons were identified in both transcriptional network models: early growth response 3 (EGR3), TSC22 domain family, member 4 (TSC22D4), interleukin enhancer-binding factor 2 (ILF2), Y-box binding protein 1 (YBX1) and MAP-kinase-activating death domain (MADD). With a high stringency threshold, the consensus across tests was achieved only for the EGR3 regulon. We identified EGR3 in the prefrontal cortex as a potential key target, robustly repressed in both BD signatures. Considering that EGR3 translates environmental stimuli into long-term changes in the brain, disruption in biological pathways involving EGR3 may induce an impaired response to stress and influence on risk for psychiatric disorders, particularly BD.en
dc.description.sponsorshipBrazilian fund CNPq/MS/SCTIE/DECIT-Pesquisas Sobre Doencas Neurodegenerativas [466989/2014-8]; Brazilian fund MCT/CNPq INCT-TM [573671/2008-7]; CAPES, Brazil; CNPq, Brazilen
dc.language.isoenen
dc.publisherNATURE PUBLISHING GROUPen
dc.relation.urlhttp://www.nature.com/doifinder/10.1038/tp.2016.78en
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License.en
dc.titleDifferential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3en
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Coll Med, Dept Basic Med Scien
dc.identifier.journalTranslational Psychiatryen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.