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The microtubule-associated protein tau is produced from a 6-kb mRNA expressed primarily in neurons. A 2-kb tau mRNA has also been characterized, which produces a tau isoform that localizes to the nucleus, and an 8-kb mRNA is expressed in the PNS. Mapping and sequencing of the human tau gene start showed that it has an unusually GC-rich 5'-untranslated region coded by a single untranslated exon (designated -1). Primer extensions and expression assays indicated that upstream of exon -1 is a promoter that is not neuron specific. This region contains consensus binding sites for transcription factors AP2, Sp1, and GCF.