O papel modulador do gene AIRE - capes

MANUSCRITOserum autoantibodies, allowing confirming this hypothesis (Anderson et al.,2002; Ramsey et al., 2002; Kuroda et al., 2005).Expression profiling of MECs isolated from Aire-knockout mice allowedthe identification of autoantigen-encoding genes, such as insulin, salivaryprotein-1 and fatty-acid-binding protein, which are under its control(Anderson et al., 2002, 2005). Meanwhile, other PTA genes, such as C-reactive protein and glutamic acid decarboxilase of 67 kDa (GAD67),appeared to be independent of Aire expression (Derbinski et al., 2005). Airealso regulates the transcription of genes that do not encode PTAs.As discussed by Mathis and Benoist (2007), a broad question still remainto be clarified on the molecular mechanisms underlying the function of Aire,that is, precisely how the protein coded by this gene promotes ectopictranscription of genes encoding PTAs and certain other proteins whilerepressing other loci.Bioinformatic re-evaluations have shown that Aire transcription mightinfluence a large number of genes, in the order of thousands rather thanhundreds, representing a significant fraction of the genome (Derbinski et al.,2005).Aire has many features of a transcription factor, sharing several domainswith known transcriptional control elements (Bottomley et al., 2001; Isaac etal., 2006) and can also associate with other transcription factors, such asCERB-binding protein (CBP), at least in vitro (Pitkanen et al., 2000, 2005).Other several characteristics of AIRE distinguish it from a “conventional”transcription factor that binds to a well defined DNA motif in an enhancer orpromoter regions of a co-ordinately regulated genes. Certainly the effect of207