Genomic organization and promoter cloning of the human X11α gene APBA1.

Hdl Handle:
http://hdl.handle.net/10147/244221
Title:
Genomic organization and promoter cloning of the human X11α gene APBA1.
Authors:
Chai, Ka-Ho; McLoughlin, Declan M; Chan, Ting Fung; Chan, Ho Yin Edwin; Lau, Kwok-Fai
Affiliation:
Biochemistry Program, School Life Sciences, The Chinese University of Hong Kong , Shatin, New Territories, Hong Kong SAR.
Citation:
Genomic organization and promoter cloning of the human X11α gene APBA1. 2012, 31 (5):651-9 DNA Cell Biol.
Journal:
DNA and cell biology
Issue Date:
May-2012
URI:
http://hdl.handle.net/10147/244221
DOI:
10.1089/dna.2011.1447
PubMed ID:
22136355
Abstract:
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:
Article
Language:
en
MeSH:
Adaptor Proteins, Signal Transducing; Animals; 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
ISSN:
1557-7430

Full metadata record

DC FieldValue Language
dc.contributor.authorChai, Ka-Hoen_GB
dc.contributor.authorMcLoughlin, Declan Men_GB
dc.contributor.authorChan, Ting Fungen_GB
dc.contributor.authorChan, Ho Yin Edwinen_GB
dc.contributor.authorLau, Kwok-Faien_GB
dc.date.accessioned2012-09-17T09:00:56Z-
dc.date.available2012-09-17T09:00:56Z-
dc.date.issued2012-05-
dc.identifier.citationGenomic organization and promoter cloning of the human X11α gene APBA1. 2012, 31 (5):651-9 DNA Cell Biol.en_GB
dc.identifier.issn1557-7430-
dc.identifier.pmid22136355-
dc.identifier.doi10.1089/dna.2011.1447-
dc.identifier.urihttp://hdl.handle.net/10147/244221-
dc.description.abstractX11α 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to DNA and cell biologyen_GB
dc.subject.meshAdaptor Proteins, Signal Transducing-
dc.subject.meshAnimals-
dc.subject.meshBase Sequence-
dc.subject.meshBlotting, Western-
dc.subject.meshCells, Cultured-
dc.subject.meshCerebral Cortex-
dc.subject.meshCloning, Molecular-
dc.subject.meshElectrophoretic Mobility Shift Assay-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshExons-
dc.subject.meshGenomics-
dc.subject.meshHumans-
dc.subject.meshLuciferases-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshNerve Tissue Proteins-
dc.subject.meshNeurons-
dc.subject.meshPromoter Regions, Genetic-
dc.subject.meshRNA, Messenger-
dc.subject.meshRats-
dc.subject.meshRats, Sprague-Dawley-
dc.subject.meshReal-Time Polymerase Chain Reaction-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshTranscription Initiation Site-
dc.titleGenomic organization and promoter cloning of the human X11α gene APBA1.en_GB
dc.typeArticleen
dc.contributor.departmentBiochemistry Program, School Life Sciences, The Chinese University of Hong Kong , Shatin, New Territories, Hong Kong SAR.en_GB
dc.identifier.journalDNA and cell biologyen_GB
dc.description.provinceLeinsteren
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