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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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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. |
format | Online Article Text |
id | pubmed-6585076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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