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MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD
Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiat...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150246/ https://www.ncbi.nlm.nih.gov/pubmed/25158004 http://dx.doi.org/10.1038/tp.2014.75 |
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author | Nieratschker, V Massart, R Gilles, M Luoni, A Suderman, M J Krumm, B Meier, S Witt, S H Nöthen, M M Suomi, S J Peus, V Scharnholz, B Dukal, H Hohmeyer, C Wolf, I A-C Cirulli, F Gass, P Sütterlin, M W Filsinger, B Laucht, M Riva, M A Rietschel, M Deuschle, M Szyf, M |
author_facet | Nieratschker, V Massart, R Gilles, M Luoni, A Suderman, M J Krumm, B Meier, S Witt, S H Nöthen, M M Suomi, S J Peus, V Scharnholz, B Dukal, H Hohmeyer, C Wolf, I A-C Cirulli, F Gass, P Sütterlin, M W Filsinger, B Laucht, M Riva, M A Rietschel, M Deuschle, M Szyf, M |
author_sort | Nieratschker, V |
collection | PubMed |
description | Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD. |
format | Online Article Text |
id | pubmed-4150246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-41502462014-09-03 MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD Nieratschker, V Massart, R Gilles, M Luoni, A Suderman, M J Krumm, B Meier, S Witt, S H Nöthen, M M Suomi, S J Peus, V Scharnholz, B Dukal, H Hohmeyer, C Wolf, I A-C Cirulli, F Gass, P Sütterlin, M W Filsinger, B Laucht, M Riva, M A Rietschel, M Deuschle, M Szyf, M Transl Psychiatry Original Article Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD. Nature Publishing Group 2014-08 2014-08-26 /pmc/articles/PMC4150246/ /pubmed/25158004 http://dx.doi.org/10.1038/tp.2014.75 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Original Article Nieratschker, V Massart, R Gilles, M Luoni, A Suderman, M J Krumm, B Meier, S Witt, S H Nöthen, M M Suomi, S J Peus, V Scharnholz, B Dukal, H Hohmeyer, C Wolf, I A-C Cirulli, F Gass, P Sütterlin, M W Filsinger, B Laucht, M Riva, M A Rietschel, M Deuschle, M Szyf, M MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD |
title | MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD |
title_full | MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD |
title_fullStr | MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD |
title_full_unstemmed | MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD |
title_short | MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD |
title_sort | morc1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with mdd |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150246/ https://www.ncbi.nlm.nih.gov/pubmed/25158004 http://dx.doi.org/10.1038/tp.2014.75 |
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