Tau promoter confers neuronal specificity and binds Sp1 and AP-2

Tau, a microtubule-associated protein, is encoded by a single gene, whose e xpression is primarily neuronal. In this work, we defined an 80-bp region o f the tau promoter that confers tau protein with neuronal expression. This fragment works in conjunction with an endogenous initiation region to activ ate neuronal precursor-specific transcription of the tau promoter and works independently of this initiation region to confer nerve growth factor indu cibility. Furthermore, this 80-bp fragment binds both Sp1 and AP-2 proteins . DNase I footprint analysis revealed a third protein binding region at the center of this 80-bp fragment in neuronal cells. Mutation within any of th ese three protein binding sites decreases transcriptional activation of the tau gene. Comprehension of the interactions that occur between cis- and tr ans-regulatory elements of the tau promoter is important to understand the regulation of tau expression during normal development and changes that may occur in many cases of dementia, including Alzheimer's disease.