Peer-reviewed
AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells
Irena Oven (Author), Naděžda Brdičková (Author), Jiři Kohoutek (Author), Tomaž. Vaupotič (Author), Mojca Narat (Author), Matija B. Peterlin (Author)
Aire is transcriptional activator that directs the ectopic expression of many tissue-specific genes in medullary thymic epithelial cells, which plays an important role in the negative selection of autoreactive T cells. However, its mechanism of action remains poorly understood. In this study, we found that AIRE regulates the step of elongation rather than initiation of RNA polymerase II. For these cells, AIRE activated the ectopic transcription of insulin and salivary protein 1 genes. Indeed, by chromatin immunoprecipitation, we found that RNA polymerase II was already engaged in these promoters but was unable to elongate in the absence of AIRE. Moreover, the genetic inactivation of cyclin T1 from P-TEFb abolished the transcription of AIRE-responsive genes and led to lymphoctic infiltration of lacrimal and salivary glands in the CycT1[up]--/-- mouse. Our findings reveal critical steps by which AIRE regulates the transcription of genes that control tolerance in the thymus
Article, English, 2007