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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-05-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18461137/pdf/?tool=EBI |
| _version_ | 1818826896187588608 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T00:34:56Z |
| format | Article |
| id | doaj.art-20644e04490b4354bc9a449488f38d1a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T00:34:56Z |
| publishDate | 2008-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-20644e04490b4354bc9a449488f38d1a2022-12-21T20:44:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-05-0135e208510.1371/journal.pone.0002085Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.Patrick O McGowanAya SasakiTony C T HuangAlexander UnterbergerMatthew SudermanCarl ErnstMichael J MeaneyGustavo TureckiMoshe Szyf<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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18461137/pdf/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18461137/pdf/?tool=EBI |
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