Evidence for a network transcriptional control of promiscuous gene expression in medullary thymic epithelial cells
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
---|---|
Data(s) |
19/10/2012
19/10/2012
2009
|
Resumo |
The 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. (C) 2009 Elsevier Ltd. All rights reserved. Fundacao de Amparo A Pesquisa do Estado de Sao Paulo (Fapesp, Sao Paulo, Brazil) Fundacao Carlos Chagas Filho de Amparo A Pesquisa no Estado do Rio de Janeiro (Faperj, Rio de Janeiro, Brazil) Conselho Nacional de Desenvolvimento Ciendfico e Tecnologico (CNPq, Brasilia, Brazil) |
Identificador |
MOLECULAR IMMUNOLOGY, v.46, n.16, p.3240-3244, 2009 0161-5890 http://producao.usp.br/handle/BDPI/23943 10.1016/j.molimm.2009.08.002 |
Idioma(s) |
eng |
Publicador |
PERGAMON-ELSEVIER SCIENCE LTD |
Relação |
Molecular Immunology |
Direitos |
restrictedAccess Copyright PERGAMON-ELSEVIER SCIENCE LTD |
Palavras-Chave | #Thymus #Medullary thymic epithelia] cells #Promiscuous gene expression #Aire #Gene network #Central T cell tolerance #Autoantigen #Autoimmunity #AUTOIMMUNE REGULATOR AIRE #CENTRAL TOLERANCE #BINDING PROTEIN #SELF #DNA #PATTERNS #Biochemistry & Molecular Biology #Immunology |
Tipo |
article original article publishedVersion |