Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.

<h4>Background</h4>Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of r...

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Autores principales: Patrick O McGowan, Aya Sasaki, Tony C T Huang, Alexander Unterberger, Matthew Suderman, Carl Ernst, Michael J Meaney, Gustavo Turecki, Moshe Szyf
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Publicado: Public Library of Science (PLoS) 2008
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Acceso en línea:https://doaj.org/article/20644e04490b4354bc9a449488f38d1a
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spelling oai:doaj.org-article:20644e04490b4354bc9a449488f38d1a2021-11-25T06:12:36ZPromoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.1932-620310.1371/journal.pone.0002085https://doaj.org/article/20644e04490b4354bc9a449488f38d1a2008-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18461137/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription.<h4>Methodology/principal findings</h4>We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor.<h4>Conclusions/significance</h4>This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.Patrick O McGowanAya SasakiTony C T HuangAlexander UnterbergerMatthew SudermanCarl ErnstMichael J MeaneyGustavo TureckiMoshe SzyfPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 5, p e2085 (2008)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Patrick O McGowan
Aya Sasaki
Tony C T Huang
Alexander Unterberger
Matthew Suderman
Carl Ernst
Michael J Meaney
Gustavo Turecki
Moshe Szyf
Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.
description <h4>Background</h4>Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription.<h4>Methodology/principal findings</h4>We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor.<h4>Conclusions/significance</h4>This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.
format article
author Patrick O McGowan
Aya Sasaki
Tony C T Huang
Alexander Unterberger
Matthew Suderman
Carl Ernst
Michael J Meaney
Gustavo Turecki
Moshe Szyf
author_facet Patrick O McGowan
Aya Sasaki
Tony C T Huang
Alexander Unterberger
Matthew Suderman
Carl Ernst
Michael J Meaney
Gustavo Turecki
Moshe Szyf
author_sort Patrick O McGowan
title Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.
title_short Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.
title_full Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.
title_fullStr Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.
title_full_unstemmed Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.
title_sort promoter-wide hypermethylation of the ribosomal rna gene promoter in the suicide brain.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/20644e04490b4354bc9a449488f38d1a
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