A polymorphic antioxidant response element links NRF2/sMAF binding to enhanced MAPT expression and reduced risk of parkinsonian disorders

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A polymorphic antioxidant response element links NRF2/sMAF binding to enhanced MAPT expression and reduced risk of parkinsonian disorders. / Wang, Xuting; Campbell, Michelle R; Lacher, Sarah E; Cho, Hye-Youn; Wan, Ma; Crowl, Christopher L; Chorley, Brian N; Bond, Gareth L; Kleeberger, Steven R; Slattery, Matthew; Bell, Douglas A.

In: Cell Reports, Vol. 15, No. 4, 26.04.2016, p. 830-842.

Research output: Contribution to journalArticlepeer-review

Harvard

Wang, X, Campbell, MR, Lacher, SE, Cho, H-Y, Wan, M, Crowl, CL, Chorley, BN, Bond, GL, Kleeberger, SR, Slattery, M & Bell, DA 2016, 'A polymorphic antioxidant response element links NRF2/sMAF binding to enhanced MAPT expression and reduced risk of parkinsonian disorders', Cell Reports, vol. 15, no. 4, pp. 830-842. https://doi.org/10.1016/j.celrep.2016.03.068

APA

Wang, X., Campbell, M. R., Lacher, S. E., Cho, H-Y., Wan, M., Crowl, C. L., Chorley, B. N., Bond, G. L., Kleeberger, S. R., Slattery, M., & Bell, D. A. (2016). A polymorphic antioxidant response element links NRF2/sMAF binding to enhanced MAPT expression and reduced risk of parkinsonian disorders. Cell Reports, 15(4), 830-842. https://doi.org/10.1016/j.celrep.2016.03.068

Vancouver

Author

Wang, Xuting ; Campbell, Michelle R ; Lacher, Sarah E ; Cho, Hye-Youn ; Wan, Ma ; Crowl, Christopher L ; Chorley, Brian N ; Bond, Gareth L ; Kleeberger, Steven R ; Slattery, Matthew ; Bell, Douglas A. / A polymorphic antioxidant response element links NRF2/sMAF binding to enhanced MAPT expression and reduced risk of parkinsonian disorders. In: Cell Reports. 2016 ; Vol. 15, No. 4. pp. 830-842.

Bibtex

@article{5924553600cf4bd8bade1187bc28f93a,
title = "A polymorphic antioxidant response element links NRF2/sMAF binding to enhanced MAPT expression and reduced risk of parkinsonian disorders",
abstract = "The NRF2/sMAF protein complex regulates the oxidative stress response by occupying cis-acting enhancers containing an antioxidant response element (ARE). Integrating genome-wide maps of NRF2/sMAF occupancy with disease-susceptibility loci, we discovered eight polymorphic AREs linked to 14 highly ranked disease-risk SNPs in individuals of European ancestry. Among these SNPs was rs242561, located within a regulatory region of the MAPT gene (encoding microtubule-associated protein Tau). It was consistently occupied by NRF2/sMAF in multiple experiments and its strong-binding allele associated with higher mRNA levels in cell lines and human brain tissue. Induction of MAPT transcription by NRF2 was confirmed using a human neuroblastoma cell line and a Nrf2-deficient mouse model. Most importantly, rs242561 displayed complete linkage disequilibrium with a highly protective allele identified in multiple GWASs of progressive supranuclear palsy, Parkinson's disease, and corticobasal degeneration. These observations suggest a potential role for NRF2/sMAF in tauopathies and a possible role for NRF2 pathway activators in disease prevention.",
author = "Xuting Wang and Campbell, {Michelle R} and Lacher, {Sarah E} and Hye-Youn Cho and Ma Wan and Crowl, {Christopher L} and Chorley, {Brian N} and Bond, {Gareth L} and Kleeberger, {Steven R} and Matthew Slattery and Bell, {Douglas A}",
year = "2016",
month = apr,
day = "26",
doi = "10.1016/j.celrep.2016.03.068",
language = "English",
volume = "15",
pages = "830--842",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - A polymorphic antioxidant response element links NRF2/sMAF binding to enhanced MAPT expression and reduced risk of parkinsonian disorders

AU - Wang, Xuting

AU - Campbell, Michelle R

AU - Lacher, Sarah E

AU - Cho, Hye-Youn

AU - Wan, Ma

AU - Crowl, Christopher L

AU - Chorley, Brian N

AU - Bond, Gareth L

AU - Kleeberger, Steven R

AU - Slattery, Matthew

AU - Bell, Douglas A

PY - 2016/4/26

Y1 - 2016/4/26

N2 - The NRF2/sMAF protein complex regulates the oxidative stress response by occupying cis-acting enhancers containing an antioxidant response element (ARE). Integrating genome-wide maps of NRF2/sMAF occupancy with disease-susceptibility loci, we discovered eight polymorphic AREs linked to 14 highly ranked disease-risk SNPs in individuals of European ancestry. Among these SNPs was rs242561, located within a regulatory region of the MAPT gene (encoding microtubule-associated protein Tau). It was consistently occupied by NRF2/sMAF in multiple experiments and its strong-binding allele associated with higher mRNA levels in cell lines and human brain tissue. Induction of MAPT transcription by NRF2 was confirmed using a human neuroblastoma cell line and a Nrf2-deficient mouse model. Most importantly, rs242561 displayed complete linkage disequilibrium with a highly protective allele identified in multiple GWASs of progressive supranuclear palsy, Parkinson's disease, and corticobasal degeneration. These observations suggest a potential role for NRF2/sMAF in tauopathies and a possible role for NRF2 pathway activators in disease prevention.

AB - The NRF2/sMAF protein complex regulates the oxidative stress response by occupying cis-acting enhancers containing an antioxidant response element (ARE). Integrating genome-wide maps of NRF2/sMAF occupancy with disease-susceptibility loci, we discovered eight polymorphic AREs linked to 14 highly ranked disease-risk SNPs in individuals of European ancestry. Among these SNPs was rs242561, located within a regulatory region of the MAPT gene (encoding microtubule-associated protein Tau). It was consistently occupied by NRF2/sMAF in multiple experiments and its strong-binding allele associated with higher mRNA levels in cell lines and human brain tissue. Induction of MAPT transcription by NRF2 was confirmed using a human neuroblastoma cell line and a Nrf2-deficient mouse model. Most importantly, rs242561 displayed complete linkage disequilibrium with a highly protective allele identified in multiple GWASs of progressive supranuclear palsy, Parkinson's disease, and corticobasal degeneration. These observations suggest a potential role for NRF2/sMAF in tauopathies and a possible role for NRF2 pathway activators in disease prevention.

U2 - 10.1016/j.celrep.2016.03.068

DO - 10.1016/j.celrep.2016.03.068

M3 - Article

C2 - 27149848

VL - 15

SP - 830

EP - 842

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 4

ER -