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DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis

BACKGROUND: Drawing the epigenome landscape of Alzheimer’s disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by us...

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Autores principales: Altuna, Miren, Urdánoz-Casado, Amaya, Sánchez-Ruiz de Gordoa, Javier, Zelaya, María V., Labarga, Alberto, Lepesant, Julie M. J., Roldán, Miren, Blanco-Luquin, Idoia, Perdones, Álvaro, Larumbe, Rosa, Jericó, Ivonne, Echavarri, Carmen, Méndez-López, Iván, Di Stefano, Luisa, Mendioroz, Maite
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585076/
https://www.ncbi.nlm.nih.gov/pubmed/31217032
http://dx.doi.org/10.1186/s13148-019-0672-7
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author Altuna, Miren
Urdánoz-Casado, Amaya
Sánchez-Ruiz de Gordoa, Javier
Zelaya, María V.
Labarga, Alberto
Lepesant, Julie M. J.
Roldán, Miren
Blanco-Luquin, Idoia
Perdones, Álvaro
Larumbe, Rosa
Jericó, Ivonne
Echavarri, Carmen
Méndez-López, Iván
Di Stefano, Luisa
Mendioroz, Maite
author_facet Altuna, Miren
Urdánoz-Casado, Amaya
Sánchez-Ruiz de Gordoa, Javier
Zelaya, María V.
Labarga, Alberto
Lepesant, Julie M. J.
Roldán, Miren
Blanco-Luquin, Idoia
Perdones, Álvaro
Larumbe, Rosa
Jericó, Ivonne
Echavarri, Carmen
Méndez-López, Iván
Di Stefano, Luisa
Mendioroz, Maite
author_sort Altuna, Miren
collection PubMed
description BACKGROUND: Drawing the epigenome landscape of Alzheimer’s disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by using the Illumina 450K methylation arrays. RESULTS: Up to 118 AD-related differentially methylated positions (DMPs) were identified in the AD hippocampus, and extended mapping of specific regions was obtained by bisulfite cloning sequencing. AD-related DMPs were significantly correlated with phosphorylated tau burden. Functional analysis highlighted that AD-related DMPs were enriched in poised promoters that were not generally maintained in committed neural progenitor cells, as shown by ChiP-qPCR experiments. Interestingly, AD-related DMPs preferentially involved neurodevelopmental and neurogenesis-related genes. Finally, InterPro ontology analysis revealed enrichment in homeobox-containing transcription factors in the set of AD-related DMPs. CONCLUSIONS: These results suggest that altered DNA methylation in the AD hippocampus occurs at specific regulatory regions crucial for neural differentiation supporting the notion that adult hippocampal neurogenesis may play a role in AD through epigenetic mechanisms. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0672-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-65850762019-06-27 DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis Altuna, Miren Urdánoz-Casado, Amaya Sánchez-Ruiz de Gordoa, Javier Zelaya, María V. Labarga, Alberto Lepesant, Julie M. J. Roldán, Miren Blanco-Luquin, Idoia Perdones, Álvaro Larumbe, Rosa Jericó, Ivonne Echavarri, Carmen Méndez-López, Iván Di Stefano, Luisa Mendioroz, Maite Clin Epigenetics Research BACKGROUND: Drawing the epigenome landscape of Alzheimer’s disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by using the Illumina 450K methylation arrays. RESULTS: Up to 118 AD-related differentially methylated positions (DMPs) were identified in the AD hippocampus, and extended mapping of specific regions was obtained by bisulfite cloning sequencing. AD-related DMPs were significantly correlated with phosphorylated tau burden. Functional analysis highlighted that AD-related DMPs were enriched in poised promoters that were not generally maintained in committed neural progenitor cells, as shown by ChiP-qPCR experiments. Interestingly, AD-related DMPs preferentially involved neurodevelopmental and neurogenesis-related genes. Finally, InterPro ontology analysis revealed enrichment in homeobox-containing transcription factors in the set of AD-related DMPs. CONCLUSIONS: These results suggest that altered DNA methylation in the AD hippocampus occurs at specific regulatory regions crucial for neural differentiation supporting the notion that adult hippocampal neurogenesis may play a role in AD through epigenetic mechanisms. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0672-7) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-19 /pmc/articles/PMC6585076/ /pubmed/31217032 http://dx.doi.org/10.1186/s13148-019-0672-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Altuna, Miren
Urdánoz-Casado, Amaya
Sánchez-Ruiz de Gordoa, Javier
Zelaya, María V.
Labarga, Alberto
Lepesant, Julie M. J.
Roldán, Miren
Blanco-Luquin, Idoia
Perdones, Álvaro
Larumbe, Rosa
Jericó, Ivonne
Echavarri, Carmen
Méndez-López, Iván
Di Stefano, Luisa
Mendioroz, Maite
DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis
title DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis
title_full DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis
title_fullStr DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis
title_full_unstemmed DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis
title_short DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis
title_sort dna methylation signature of human hippocampus in alzheimer’s disease is linked to neurogenesis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585076/
https://www.ncbi.nlm.nih.gov/pubmed/31217032
http://dx.doi.org/10.1186/s13148-019-0672-7
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