Genomic organization and promoter cloning of the human X11α gene APBA1.
Affiliation
Biochemistry Program, School Life Sciences, The Chinese University of Hong Kong , Shatin, New Territories, Hong Kong SAR.Issue Date
2012-05MeSH
Adaptor Proteins, Signal TransducingAnimals
Base Sequence
Blotting, Western
Cells, Cultured
Cerebral Cortex
Cloning, Molecular
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
Exons
Genomics
Humans
Luciferases
Molecular Sequence Data
Nerve Tissue Proteins
Neurons
Promoter Regions, Genetic
RNA, Messenger
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Transcription Initiation Site
Metadata
Show full item recordCitation
Genomic organization and promoter cloning of the human X11α gene APBA1. 2012, 31 (5):651-9 DNA Cell Biol.Journal
DNA and cell biologyDOI
10.1089/dna.2011.1447PubMed ID
22136355Abstract
X11α is a brain specific multi-modular protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). Aggregation of amyloid-β peptide (Aβ), an APP cleavage product, is believed to be central to the pathogenesis of Alzheimer's disease. Recently, overexpression of X11α has been shown to reduce Aβ generation and to ameliorate memory deficit in a transgenic mouse model of Alzheimer's disease. Therefore, manipulating the expression level of X11α may provide a novel route for the treatment of Alzheimer's disease. Human X11α is encoded by the gene APBA1. As evidence suggests that X11α expression can be regulated at transcription level, we have determined the gene structure and cloned the promoter of APBA1. APBA1 spans over 244 kb on chromosome 9 and is composed of 13 exons and has multiple transcription start sites. A putative APBA1 promoter has been identified upstream of exon 1 and functional analysis revealed that this is highly active in neurons. By deletion analysis, the minimal promoter was found to be located between -224 and +14, a GC-rich region that contains a functional Sp3 binding site. In neurons, overexpression of Sp3 stimulates the APBA1 promoter while an Sp3 inhibitor suppresses the promoter activity. Moreover, inhibition of Sp3 reduces endogenous X11α expression and promotes the generation of Aβ. Our findings reveal that Sp3 play an essential role in APBA1 transcription.Item Type
ArticleLanguage
enISSN
1557-7430ae974a485f413a2113503eed53cd6c53
10.1089/dna.2011.1447
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