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 language | English |
|---|---|
| Pages (from-to) | 81-99 |
| Number of pages | 19 |
| Journal | Journal of Molecular Neuroscience |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| State | Published - May 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Characterization of the human β-secretase 2 (BACE2) 5′-flanking region
T2 - Identification of a 268-bp region as the basal BACE2 promoter
AU - Maloney, Bryan
AU - Ge, Yuan Wen
AU - Greig, Nigel H.
AU - Lahiri, Debomoy
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - Aging
KW - Amyloid
KW - Dementia
KW - Neurons
KW - Promoter
KW - Secretase
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=33744953279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33744953279&partnerID=8YFLogxK
U2 - 10.1385/JMN:29:1:81
DO - 10.1385/JMN:29:1:81
M3 - Article
C2 - 16757812
AN - SCOPUS:33744953279
VL - 29
SP - 81
EP - 99
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 1
ER -