Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants
Oncotarget
; 7(7): 7497-533, 2016. ilus, tab, graf
Article
em En
| SES-SP, SESSP-IDPCPROD, SES-SP
| ID: biblio-1065031
Biblioteca responsável:
BR79.1
Localização: BR79.1
ABSTRACT
Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome(DS) and karyotipically normal subjects (CT) - and a network-based approach forGCN analysis that allows the identification of modular transcriptional repertoires(communities) and the interactions between all the systems constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified inthese networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 genedys regulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the canonical way of thymus functioning. Conversely, DS networks represent a non-canonical way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probablydriven by epigenetic mechanisms acting at chromatin level and through the miRNAcontrol of transcriptional programs involving the networks high-hierarchy genes...
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Coleções:
06-national
/
BR
Base de dados:
SES-SP
/
SESSP-IDPCPROD
Assunto principal:
Síndrome
/
Síndrome de DiGeorge
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article