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Gene structure and organization of the human β‐secretase (BACE) promoter

Gene structure and organization of the human β‐secretase (BACE) promoter The first step in the generation of the amyloid‐β peptide (Aβ) deposited in the brains of patients with Alzheimer's disease (AD) is the processing of the larger Aβ precursor protein (APP) by an integral membrane aspartyl protease named the β‐site APP‐cleaving enzyme (BACE). We present the genomic organization of the BACE gene. BACE mRNAs are synthesized as nine exons and eight introns from a 30.6 kb region of chromosome 11q23.2–11q23.3. Regulation of BACE may play an important role in regulating the levels of Aβ produced and is therefore likely to play an important role in AD. Herein, we report the cloning and detailed analysis of 3765 nucleotides of the promoter region of BACE and 364 nucleotides of the 5′ untranslated region of the BACE mRNA (5′ UTR). Characteristic “CAAT” and “TATA” boxes are absent within 1.5 kb of the transcription start site (TSS). The promoter region and 5′ UTR contain multiple transcription factor binding sites, such as activator protein (AP)1, AP2, cAMP response element binding protein (CREB), estrogen responsive element (ERE), glucocorticoid responsive element (GRE), “GC” box, nuclear factor (NF)‐κB, signal transducer and activator of transcription (STAT)1, stimulating protein (SP)1, metal‐regulatory elements, and possible Zeste binding sites. Limited interspecies similarity was observed between the human sequence and corresponding genomic DNA from the rat and mouse sequences, but several transcription factor‐binding sites are conserved. Thus, the BACE gene contains basal regulatory elements, inducible features and sites for regulated activity by various transcription factors. These results identify the important regions for functional analysis of the binding domains and neuron‐specific expression (1). Such a study will allow us to further examine the possible role of changes in the promoter of BACE in AD pathogenesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The FASEB journal Wiley

Gene structure and organization of the human β‐secretase (BACE) promoter

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References (46)

Publisher
Wiley
Copyright
© Federation of American Societies for Experimental Biology
ISSN
0892-6638
eISSN
1530-6860
DOI
10.1096/fj.03-1378fje
Publisher site
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Abstract

The first step in the generation of the amyloid‐β peptide (Aβ) deposited in the brains of patients with Alzheimer's disease (AD) is the processing of the larger Aβ precursor protein (APP) by an integral membrane aspartyl protease named the β‐site APP‐cleaving enzyme (BACE). We present the genomic organization of the BACE gene. BACE mRNAs are synthesized as nine exons and eight introns from a 30.6 kb region of chromosome 11q23.2–11q23.3. Regulation of BACE may play an important role in regulating the levels of Aβ produced and is therefore likely to play an important role in AD. Herein, we report the cloning and detailed analysis of 3765 nucleotides of the promoter region of BACE and 364 nucleotides of the 5′ untranslated region of the BACE mRNA (5′ UTR). Characteristic “CAAT” and “TATA” boxes are absent within 1.5 kb of the transcription start site (TSS). The promoter region and 5′ UTR contain multiple transcription factor binding sites, such as activator protein (AP)1, AP2, cAMP response element binding protein (CREB), estrogen responsive element (ERE), glucocorticoid responsive element (GRE), “GC” box, nuclear factor (NF)‐κB, signal transducer and activator of transcription (STAT)1, stimulating protein (SP)1, metal‐regulatory elements, and possible Zeste binding sites. Limited interspecies similarity was observed between the human sequence and corresponding genomic DNA from the rat and mouse sequences, but several transcription factor‐binding sites are conserved. Thus, the BACE gene contains basal regulatory elements, inducible features and sites for regulated activity by various transcription factors. These results identify the important regions for functional analysis of the binding domains and neuron‐specific expression (1). Such a study will allow us to further examine the possible role of changes in the promoter of BACE in AD pathogenesis.

Journal

The FASEB journal – Wiley

Published: Jun 1, 2004

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