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O papel modulador do gene AIRE - capes

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MANUSCRITOwere analyzed using the Multiexperiment Viewer (MeV) software (version 3.1;available online at (http://www.tm4.org/mev.html) [Smyth, 2004].The differentially expressed <strong>gene</strong>s (induced or repressed) between controland Aire silenced mTECs were identified by using the significance analysis ofmicroarrays program (SAM) (Tusher et al., 2001) considering only those <strong>gene</strong>spresenting both FDR (false discovery rate) and p value ≤ 0.01.To analyze the <strong>gene</strong> expression profiling we used an unsupervisedhierarchical clustering method that grouped <strong>gene</strong>s on the vertical axis andsamples on the horizontal axis, on the basis of similarity in their expressionpatterns. The similarities and dissimilarities in <strong>gene</strong> expression are presented asdendrograms, in which the pattern and length of the branches reflect therelatedness of the samples or <strong>gene</strong>s, and as heat maps (Eisen et al., 1989)(Cluster version 3.0 and Java Tree View (http://rana.lbl.gov/EisenSoftware.htm).Determination of PGE in mTECsPGE was identified on the basis of data from microarray analysis of thedifferent mouse organs using combined information from the public databaseGNF Gene expression Atlas (http://symatlas.gnf.org/SymAtlas). This data bankshows <strong>gene</strong> expression in more than 60 mouse tissue/organs, as assessed by<strong>gene</strong> array analysis using Affymetrix microarrays. Data information includesGenBank accession, chromosomal location, tissue/organ representation andmolecular/biological function of each <strong>gene</strong> analyzed.In this study, only the promiscuous <strong>gene</strong>s of which the expression wasdetected in different organs or tissues and of which the expression levels weregreater than median in relation to all other organs which appear in the GNFAtlas were considered. The modulation of transcription levels (repression or211

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