Characterization of the human β-secretase 2 (BACE2) 5′-flanking region: Identification of a 268-bp region as the basal BACE2 promoter

Bryan Maloney, Yuan Wen Ge, Nigel H. Greig, Debomoy Lahiri

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The main characteristic of Alzheimer's disease (AD) is brain deposition of the β-amyloid (Aβ) peptide, generated endoproteolytically from Aβ precursor protein (APP) by β- and γ-secretases. A transmembrane aspartyl protease, β-APP-cleaving enzyme (BACE1), was identified as β-secretase. Although BACE1 cleaves APP at the β-secretase site, the role of its homolog, β-secretase 2 (BACE2) is poorly understood. We report the mRNAexpression profile, DNAsequence, and molecular characterization of the BACE2 gene, located on chromosome 21q22.3. The BACE2 gene expresses more strongly in peripheral tissues, although BACE2 mRNA is found in the majority of brain regions, including the postcentral gyrus and temporal lobe. Characterization of 2932 bp of the BACE2 5′-flanking region (GC content of 55%), reveals the absence of canonical CCAAT and TATA boxes within 1 kb of the transcription start site (TSS). The sequence lacks significant internal repeats and has a housekeeping gene structure. Two active regions of the BACE2 promoter determine its basal expression and cell-type specificity. The proximal region (-31/+238) likely determines general basal expression, and the distal region (-2618/-1513), cell-type specificity. Several putative transcription factor sites, particularly SP1, Oct-1, and HES-1, are predicted to be within 1 kb of the TSS. On either side of the proximal promoter region, two negative regulatory domains might reduce BACE2 expression under an induced condition. The BACE2 5′-flanking region is likely to be highly regulated and expressed in a tissue type-specific manner.

Original languageEnglish
Pages (from-to)81-99
Number of pages19
JournalJournal of Molecular Neuroscience
Volume29
Issue number1
DOIs
StatePublished - May 2006

Fingerprint

Amyloid Precursor Protein Secretases
5' Flanking Region
Protein Precursors
Genes
Transcription Initiation Site
Genetic Promoter Regions
Brain
Tissue
Aspartic Acid Proteases
TATA Box
Somatosensory Cortex
Essential Genes
Base Composition
Temporal Lobe
Chromosomes
Amyloid
Alzheimer Disease
Transcription Factors
Messenger RNA
Peptides

Keywords

  • Aging
  • Amyloid
  • Dementia
  • Neurons
  • Promoter
  • Secretase
  • Transcription factors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

Characterization of the human β-secretase 2 (BACE2) 5′-flanking region : Identification of a 268-bp region as the basal BACE2 promoter. / Maloney, Bryan; Ge, Yuan Wen; Greig, Nigel H.; Lahiri, Debomoy.

In: Journal of Molecular Neuroscience, Vol. 29, No. 1, 05.2006, p. 81-99.

Research output: Contribution to journalArticle

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abstract = "The main characteristic of Alzheimer's disease (AD) is brain deposition of the β-amyloid (Aβ) peptide, generated endoproteolytically from Aβ precursor protein (APP) by β- and γ-secretases. A transmembrane aspartyl protease, β-APP-cleaving enzyme (BACE1), was identified as β-secretase. Although BACE1 cleaves APP at the β-secretase site, the role of its homolog, β-secretase 2 (BACE2) is poorly understood. We report the mRNAexpression profile, DNAsequence, and molecular characterization of the BACE2 gene, located on chromosome 21q22.3. The BACE2 gene expresses more strongly in peripheral tissues, although BACE2 mRNA is found in the majority of brain regions, including the postcentral gyrus and temporal lobe. Characterization of 2932 bp of the BACE2 5′-flanking region (GC content of 55{\%}), reveals the absence of canonical CCAAT and TATA boxes within 1 kb of the transcription start site (TSS). The sequence lacks significant internal repeats and has a housekeeping gene structure. Two active regions of the BACE2 promoter determine its basal expression and cell-type specificity. The proximal region (-31/+238) likely determines general basal expression, and the distal region (-2618/-1513), cell-type specificity. Several putative transcription factor sites, particularly SP1, Oct-1, and HES-1, are predicted to be within 1 kb of the TSS. On either side of the proximal promoter region, two negative regulatory domains might reduce BACE2 expression under an induced condition. The BACE2 5′-flanking region is likely to be highly regulated and expressed in a tissue type-specific manner.",
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