title: Two novel DNA motifs are essential for BACE1 gene transcription.
abstract: BACE1 gene encodes for β-Site amyloid β precursor protein (APP)-cleaving enzyme1, which is required for generating amyloid β protein(Aβ). Deposition of Aβ 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.
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Meng
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Songyang
authors.initials: S
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Tingyu
authors.initials: T
authors.lastname: Li
authors.affiliation: 1] Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China [2] Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, University of British Columbia, Vancouver, British Columbia, V6T1Z3, Canada.
authors.forename: Weihong
authors.initials: W
authors.lastname: Song
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, 136 ZhongshanEr Lu, Yuzhong District, Chongqing 400014, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Zhou
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000235:genetics*; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D020218:Response Elements; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human