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The Microtubule-associated protein tau (MAPT) gene promoter is the regulatory DNA sequence responsible for controlling the expression of the tau protein in neurons (PubMed: 32814900). Tau is essential for stabilizing microtubules in axons, but its overexpression or aggregation is a hallmark of neurodegenerative tauopathies, including Alzheimer's disease (UniProt: P10636; PubMed: 31511698). Targeting the MAPT promoter aims to reduce the overall production of tau protein at the transcriptional level, thereby preventing the formation of toxic aggregates (PubMed: 30643246). Therapeutic strategies include the use of engineered transcription factors, such as zinc finger proteins (e.g., ST-501), to bind the promoter and repress transcription (Sangamo Therapeutics, 2023). Reducing tau expression is considered a promising approach to slow or halt disease progression in patients with various forms of dementia.
Transcriptional repression via sequence-specific DNA binding and recruitment of epigenetic silencers
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