Transcriptional complexes that control the expression of anergy-associated genes
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In T cells, anergy can be induced following T cell receptor engagement in the absence of co-stimulation. Under these conditions, NFAT proteins are activated in the absence of full activation of their transcriptional partners (i.e. AP-1 proteins), leading to the expression of a specific set of anergy-associated genes. Several lines of evidence suggest that NFAT proteins may regulate the expression of many of those genes, however, the nature of the complexes responsible for the induction of this new program of gene expression are unknown. We show that NFAT homodimers are the transcriptional complexes that activate the expression of at least two anergy-inducing genes, Grail and Caspase-3. NFAT dimers bind the Grail promoter at two different sites and induce the expression of this gene. Our results not only identify the first known biological function for NFAT homodimers but also establish the different nature of the NFAT-containing complexes that induce anergy from those activated during a productive immune response, and set the basis for the design of immunomodulatory strategies that may specifically target each of them.