Two novel DNA motifs are essential for BACE1 gene transcription

BACE1 gene encodes for beta-Site amyloid beta precursor protein (APP)-cleaving enzyme1, which is required for generating amyloid b protein(A beta). Deposition of A beta in brain plays an essential role in Alzheimer's Disease (AD) pathogenesis. BACE1 gene has a tissue-specific expression pattern and its expression is tightly regulated at transcriptional level. Core promoter is a minimal DNA sequence to direct transcription initiation and serves as a converging platform for the vast network of regulatory events. Here we identified the core promoter of human BACE1 gene, which is a 71 nucleotides region absent of typical known core promoter elements and is sufficient to initiate a basal transcription. Two novel DNA motifs, designated TCE1 and TCE2, were found to be involved in activating the transcription of human BACE1 gene in a synergistic way. Two single nucleotide mutations in these motifs completely abolished the promoter activity. In conclusion, our studies have demonstrated that novel DNA motif TCE1 and TCE2 in human BACE1 gene promoter are two essential cis-acting elements for BACE1 gene transcription. Studies on how these two motifs being regulated by different stimuli could provide insights into the molecular mechanisms underlying AD pathogenesis and pharmaceutical potentials of targeting these motifs for AD treatment.