Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE

Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE

Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer...

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Main Authors: Bekris, L.M., Lutz, F., Yu, C.E.
Format: Online
Language:English
Published: 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266441/
id pubmed-3266441
recordtype oai_dc
spelling pubmed-32664412012-07-01 Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE Bekris, L.M. Lutz, F. Yu, C.E. Article Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer region genetic variation on regional gene promoter activity. Luciferase reporter constructs containing haplotypes of APOE locus gene promoters; APOE, APOC1, and TOMM40, and regional putative enhancers; TOMM40 IVS2-4, TOMM40 IVS6 poly-T, as well as previously described enhancers; ME1, or BCR, were evaluated for their effects on luciferase activity in 3 human cell lines. Results of this investigation demonstrate that in SHSY5Y cells, the APOE promoter is significantly influenced by the TOMM40 IVS2-4 and ME1 and the TOMM40 promoter is significantly influenced by the TOMM40 IVS6 poly-T, ME1 and BCR. In HepG2 cells, theTOMM40 promoter is significantly influenced by all four enhancers, whereas the APOE promoter is not influenced by any of the enhancers. The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type suggesting that a complex transcriptional regulatory structure modulates regional expression. 2011-11-17 2012-01 /pmc/articles/PMC3266441/ /pubmed/22089642 http://dx.doi.org/10.1038/jhg.2011.123 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Bekris, L.M.
Lutz, F.
Yu, C.E.
spellingShingle Bekris, L.M.
Lutz, F.
Yu, C.E.
Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE
author_facet Bekris, L.M.
Lutz, F.
Yu, C.E.
author_sort Bekris, L.M.
title Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE
title_short Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE
title_full Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE
title_fullStr Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE
title_full_unstemmed Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE
title_sort functional analysis of apoe locus genetic variation implicates regional enhancers in the regulation of both tomm40 and apoe
description Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer region genetic variation on regional gene promoter activity. Luciferase reporter constructs containing haplotypes of APOE locus gene promoters; APOE, APOC1, and TOMM40, and regional putative enhancers; TOMM40 IVS2-4, TOMM40 IVS6 poly-T, as well as previously described enhancers; ME1, or BCR, were evaluated for their effects on luciferase activity in 3 human cell lines. Results of this investigation demonstrate that in SHSY5Y cells, the APOE promoter is significantly influenced by the TOMM40 IVS2-4 and ME1 and the TOMM40 promoter is significantly influenced by the TOMM40 IVS6 poly-T, ME1 and BCR. In HepG2 cells, theTOMM40 promoter is significantly influenced by all four enhancers, whereas the APOE promoter is not influenced by any of the enhancers. The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type suggesting that a complex transcriptional regulatory structure modulates regional expression.
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266441/
_version_ 1611502267043676160

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