Tau promoter confers neuronal specificity and binds Sp1 and AP-2.
Tau, a microtubule-associated protein, is encoded by a single gene, whose expression is primarily neuronal. In this work, we defined an 80-bp region of the tau promoter that confers tau protein with neuronal expression. This fragment works in conjunction with an endogenous initiation region to activate neuronal precursor-specific transcription of the tau promoter and works independently of this initiation region to confer nerve growth factor inducibility. Furthermore, this 80-bp fragment binds both Sp1 and AP-2 proteins. DNase I foot-print analysis revealed a third protein binding region at the center of this 80-bp fragment in neuronal cells. Mutation within any of these three protein binding sites decreases transcriptional activation of the tau gene. Comprehension of the interactions that occur between cis- and trans-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.
Heicklen-Klein
A
A
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Ginzburg
I
I
D051698:Activating Transcription Factor 2; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive / Q000235:genetics; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics; D002999:Clone Cells; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018983:DNA Footprinting; D004591:Electrophoresis, Polyacrylamide Gel; D016297:Mutagenesis, Site-Directed; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D020218:Response Elements / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics*
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D016875:tau Proteins; D020932:Nerve Growth Factor