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Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3.
Pfaffenseller, B; da Silva Magalhães, P V; De Bastiani, M A; Castro, M A A; Gallitano, A L; Kapczinski, F; Klamt, F.
Afiliação
  • Pfaffenseller B; Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
  • da Silva Magalhães PV; Laboratory of Cellular Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • De Bastiani MA; Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
  • Castro MA; Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • Gallitano AL; Laboratory of Cellular Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • Kapczinski F; Bioinformatics and Systems Biology Laboratory, Federal University of Paraná, Polytechnic Center, Curitiba, Brazil.
  • Klamt F; Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, USA.
Transl Psychiatry ; 6: e805, 2016 05 10.
Article em En | MEDLINE | ID: mdl-27163206
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Transtorno Bipolar / Córtex Pré-Frontal / Fatores de Troca do Nucleotídeo Guanina / Proteína do Fator Nuclear 45 / Proteína 1 de Ligação a Y-Box / Proteína 3 de Resposta de Crescimento Precoce / Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Transl Psychiatry Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Transtorno Bipolar / Córtex Pré-Frontal / Fatores de Troca do Nucleotídeo Guanina / Proteína do Fator Nuclear 45 / Proteína 1 de Ligação a Y-Box / Proteína 3 de Resposta de Crescimento Precoce / Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Transl Psychiatry Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos