Evidence for a network transcriptional control of promiscuous gene expression in medullary thymic epithelial cells

dc.creatorMacedo, Cláudia
dc.creatorEvangelista, Adriane F.
dc.creatorMagalhães, Danielle A.
dc.creatorFornari, Thaís A.
dc.creatorLinhares, Leandra L.
dc.creatorJunta, Cristina M.
dc.creatorSilva, Guilherme L.
dc.creatorSakamoto-Hojo, Elza T.
dc.creatorDonadi, Eduardo A.
dc.creatorSavino, Wilson
dc.creatorPassos, Geraldo A. S.
dc.date2018-08-16T17:21:27Z
dc.date2018-08-16T17:21:27Z
dc.date2009
dc.date.accessioned2023-09-26T23:47:00Z
dc.date.available2023-09-26T23:47:00Z
dc.identifierMACEDO, Cláudia; et al. Evidence for a network transcriptional control of promiscuous gene expression in medullary thymic epithelial cells. Molecular Immunology, v.46, p.3240–3244, 2009.
dc.identifier0161-5890
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/28194
dc.identifier10.1016/j.molimm.2009.08.002
dc.identifier1872-9142
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8894159
dc.descriptionThe expression of peripheral tissue antigens (PTAs) in the thymus by medullary thymic epithelial cells (mTECs) is essential for the central self-tolerance in the generation of the T cell repertoire. Due to heterogeneity of autoantigen representation, this phenomenon has been termed promiscuous gene expression (PGE), in which the autoimmune regulator (Aire) gene plays a key role as a transcription factor in part of these genes. Here we used a microarray strategy to access PGE in cultured murine CD80+ 3.10 mTEC line. Hierarchical clustering of the data allowed observation that PTA genes were differentially expressed being possible to found their respective induced or repressed mRNAs. To further investigate the control of PGE, we tested the hypothesis that genes involved in this phenomenon might also be modulated by transcriptional network. We then reconstructed such network based on the microarray expression data, featuring the guanylate cyclase 2d (Gucy2d) gene as a main node. In such condition, we established 167 positive and negative interactions with downstream PTA genes. Silencing Aire by RNA interference, Gucy2d while down regulated established a larger number (355) of interactions with PTA genes. T- and G-boxes corresponding to AIRE protein binding sites located upstream to ATG codon of Gucy2d supports this effect. These findings provide evidence that Aire plays a role in association with Gucy2d, which is connected to several PTA genes and establishes a cascade-like transcriptional control of promiscuous gene expression in mTEC cells.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier 12 Months
dc.rightsrestricted access
dc.subjectTimo
dc.subjectRedes Reguladoras de Genes
dc.subjectAutoimunidade
dc.subjectAutoantígeno
dc.subjectExpressão Gênica
dc.subjectCélulas epiteliais do timo medular
dc.subjectExpressão gênica promíscua
dc.subjectTolerância central da célula T
dc.subjectThymus
dc.subjectMedullary thymic epithelial cells
dc.subjectPromiscuous gene expression
dc.subjectAire
dc.subjectGene network
dc.subjectCentral T cell tolerance
dc.subjectAutoantigen
dc.subjectAutoimmunity
dc.titleEvidence for a network transcriptional control of promiscuous gene expression in medullary thymic epithelial cells
dc.typeArticle


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