Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain
PLoS ONEPublished 6 May 2008Open access
Patrick O. McGowan, Aya Sasaki, Tony Chieh‐Ting Huang, Alexander Unterberger, Matthew Suderman, Carl Ernst
Citations374
SJR quartileQ1
SJR score0.80
SNIP1.07
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TL;DR
This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain and the data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.
Abstract
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.
Keywords
Biochemistry, Genetics and Molecular Biology
Journal of Educational StatisticsStatistical Methods for Meta-Analysis
10,479 Citations1988Stanley Wasserman, Larry V. Hedges +1 more
Nature NeuroscienceEpigenetic programming by maternal behavior
6,148 Citations2004Ian C.G. Weaver, Nadia Cervoni +7 more
It is shown that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible, suggesting a causal relation among epigenomicState, GR expression and the maternal effect on stress responses in the offspring.
Archives of General PsychiatryThe Structured Clinical Interview for DSM-III-R (SCID)
4,364 Citations1992Robert L. Spitzer
The history, rationale, and development of the Structured Clinical Interview for DSM-III-R (SCID) is described, which is a semistructured interview for making the major Axis I DSM- III-R diagnoses.
Proceedings of the National Academy of SciencesA genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands.
3,265 Citations1992Marianne Frommer, Louise E. McDonald +6 more
A genomic sequencing method is reported that provides positive identification of 5-methylcytosine residues and yields strand-specific sequences of individual molecules in genomic DNA, which suggests that the high methylation level of single-copy sequences in sperm may be locally modulated by binding of protein factors in germ-line cells.
ScienceDNA Methylation and Gene Function
2,093 Citations1980Aharon Razin, Arthur D. Riggs
There is now reason to believe, from recent studies, that DNA methylation is a key element in the hierarchy of control mechanisms that govern vertebrate gene function and differentiation.
Nucleic Acids ResearchHigh sensitivity mapping of methylated cytosines
1,870 Citations1994J.CIark Susan, Ewen M. Harrison +2 more
A genomic sequencing technique which is capable of detecting every methylated cytosine on both strands of any target sequence, using DNA isolated from fewer than 100 cells is developed.
Nature reviews. NeuroscienceEpigenetic regulation in psychiatric disorders
1,393 Citations2007Nadia M. Tsankova, William Renthal +2 more
CellMeCP2 Is a Transcriptional Repressor with Abundant Binding Sites in Genomic Chromatin
1,291 Citations1997Xinsheng Nan, Francisco J. Campoy +1 more
Transient transfection using fusions with the GAL4 DNA binding domain identified a region of MeCP2 that is capable of long-range repression in vivo and suggest a role as a global transcriptional repressor in vertebrate genomes.
Archives of General PsychiatryA Prospective Investigation of Major Depressive Disorder and Comorbidity in Abused and Neglected Children Grown Up
1,065 Citations2007Cathy Spatz Widom, Kimberly DuMont +1 more
The need for clinicians to increase efforts to detect and treat depression in physically abused and neglected children is supported, as child abuse and neglect were associated with an increased risk for current MDD.
Dialogues in Clinical NeuroscienceEnvironmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome
925 Citations2005Michael J. Meaney, Moshe Szyf
It is demonstrated that the structural modifications of the DNA can be established through environmental programming and that, in spite of the inherent stability of this epigenomic marker, it is dynamic and potentially reversible.
American Journal of PsychiatryChildhood Trauma Associated With Smaller Hippocampal Volume in Women With Major Depression
815 Citations2002Meena Vythilingam, Christine Heim +10 more
A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood.
Journal of the American Academy of Child & Adolescent PsychiatryChildhood Sexual Abuse and Psychiatric Disorder in Young Adulthood: II. Psychiatric Outcomes of Childhood Sexual Abuse
809 Citations1996David M. Fergusson, L. John Horwood +1 more
CSA, and particularly severe CSA, was associated with increased risk of psychiatric disorder in young adults even when due allowance was made for prospectively measured confounding factors.
The EMBO JournalCpG methylation, chromatin structure and gene silencing—a three‐way connection
798 Citations1998Aharon Razin
Molecular link between methyl groups on the DNA and the positioning of nucleosomes to form an inactive chromatin configuration was missing and recent experimental data may shed light on this molecular link.
Journal of Personality DisordersThe Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II). Part I: Description
706 Citations1995Michael B. First, Robert L. Spitzer +2 more
EndocrinologyMaternal Care Associated with Methylation of the Estrogen Receptor-α1b Promoter and Estrogen Receptor-α Expression in the Medial Preoptic Area of Female Offspring
676 Citations2006Frances A. Champagne, Ian C.G. Weaver +4 more
In the present studies, cross-fostering confirmed an association between maternal care and ERα expression in the MPOA; the biological offspring of low LG mothers fostered at birth to high LG dams show increased ERα Expression in theMPOA.
Journal of Child Psychology and PsychiatryChildhood Experience of Care and Abuse (CECA): A Retrospective Interview Measure
587 Citations1994Antonia Bifulco, George W. Brown +1 more
The development of a retrospective, investigator-based interview measure of Childhood Experience of Care and Abuse (CECA) used with two community samples of adults in London is described and the component ratings are shown to have satisfactory inter-rater reliability and also validity as determined by agreement between sisters' independent accounts.
American Journal of PsychiatryRisk Factors for Suicide Completion in Major Depression: A Case-Control Study of Impulsive and Aggressive Behaviors in Men
582 Citations2005Alexandre Dumais, Alain Lesage +8 more
Impulsive-aggressive personality disorders and alcohol abuse/dependence were two independent predictors of suicide in major depression, and impulsive and aggressive behaviors seem to underlie these risk factors.
Annals of Internal MedicineA Current Perspective of Suicide and Attempted Suicide
567 Citations2002J. John Mann
The neurobiological correlates of the stressors and the diathesis for suicidal behavior are described and the factors that determined inclusion in this review were superiority of research design, quality of psychometrics, and adequate representation of major points of view.
Proceedings of the National Academy of SciencesReelin promoter hypermethylation in schizophrenia
552 Citations2005Dennis R. Grayson, Xiaomei Jia +5 more
The data show that this promoter region has positive and negative properties and that the function of this complex cis element relates to its methylation status.
Environmental and Molecular MutagenesisThe social environment and the epigenome
537 Citations2007Moshe Szyf, Patrick O. McGowan +1 more
It is speculated that exposures to different environmental toxins alters long‐established epigenetic programs in the brain as well as other tissues leading to late‐onset disease.
Human Molecular GeneticsHypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder
460 Citations2006Hamid M. Abdolmaleky, Kuang‐Hung Cheng +14 more
It is suggested that MB-COMT over-expression due to promoter hypomethylation and/or hyperactive allele of COMT may increase dopamine degradation in the frontal lobe providing a molecular basis for the shared symptoms of schizophrenia and bipolar disorder.
Journal of NeuroscienceRibosome Dysfunction Is an Early Event in Alzheimer's Disease
452 Citations2005Qunxing Ding, William R. Markesbery +3 more
It is reported that in multiple cortical areas of MCI and AD subjects, there is a significant impairment in ribosome function that is not observed in the cerebellum of the same subjects, and this data directly demonstrate that the polyribosome complex is adversely affected early in the development of AD.
Nucleic Acids ResearchCpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2
424 Citations1990Michael J. Comb, Howard M. Goodman
The results suggest that CpG methylation inhibits proenkephalin gene expression by directly interfering with the binding of a positively acting transcription factor previously shown to be essential for maximal basal, cAMP, and TPA inducible transcription.
Journal of Biological ChemistryValproate Induces Replication-independent Active DNA Demethylation
345 Citations2003Nancy Detich, Veronica Bovenzi +1 more
The data support a new mechanism of action for VPA as enhancing intracellular demethylase activity through its effects on histone acetylation and raises the possibility that DNA methylation is reversible independent of DNA replication by commonly prescribed drugs.
Genome ResearchGenomic architecture and inheritance of human ribosomal RNA gene clusters
318 Citations2007Dawn Michelle Stults, Michael W. Killen +2 more
Analysis of these rDNA fingerprints in multigenerational human families demonstrates that the rDNA clusters are subject to meiotic rearrangement at a frequency >10% per cluster, per meiosis, and may serve as a unique paradigm of potential human genomic plasticity.
Archives of General PsychiatrySuicide in Twins
262 Citations1991Alec Roy
Twin data suggest that genetic factors related to suicide may largely represent a genetic predisposition for the psychiatric disorders associated with suicide, however, they leave open the question of whether there may be an independent genetic component for suicide.
Journal of Psychiatry and NeuroscienceDissecting the suicide phenotype: the role of impulsive–aggressive behaviours
257 Citations2005Gustavo Turecki
There is a need to better understand the mechanisms mediating suicide among individuals with no history of impulsive-aggressive behaviors, and whether these mechanisms could be useful in molecular genetic studies of suicide.
CarcinogenesisValproate induces widespread epigenetic reprogramming which involves demethylation of specific genes
256 Citations2006Snezana Milutinovic, Ana C. D’Alessio +2 more
The data supports the concept that chromatin acetylation and DNA methylation are found in a dynamic interrelation and that the consequences of HDAC inhibitors are not limited to changes in histone acetylations but that they also bring about a change in the state of modification of DNA.
Molecular CellMolecular Mechanisms Mediating Methylation-Dependent Silencing of Ribosomal Gene Transcription
246 Citations2001Raffaella Santoro, Ingrid Grummt
Ch chromatin immunoprecipitation assays demonstrate that methylation of the cytosine at -133 inhibits binding of the transcription factor UBF to nucleosomal rDNA, thereby preventing initiation complex formation and methylation may be a mechanism to inactivate rDNA genes and propagate transcriptional silencing through cell division.
Journal of NeuroscienceDNA Methylation Status of<i>SOX10</i>Correlates with Its Downregulation and Oligodendrocyte Dysfunction in Schizophrenia
243 Citations2005Kazuya Iwamoto, Miki Bundo +5 more
It is found that the cytosine-guanine dinucleotide (CpG) island of sex-determining region Y-box containing gene 10 (SOX10), an oligodendrocyte-specific transcription factor, tended to be highly methylated in brains of patients with schizophrenia, correlated with reduced expression of SOX10.
Journal of Biological ChemistryRole of Human Ribosomal RNA (rRNA) Promoter Methylation and of Methyl-CpG-binding Protein MBD2 in the Suppression of rRNA Gene Expression
209 Citations2004Kalpana Ghoshal, Sarmila Majumder +6 more
Chromatin immunoprecipitation analysis confirmed predominant association of MBD2 with the endogenous methylated rRNA promoter, which suggests a selective role for MBD1 and MBD3 in the methylation-mediated inhibition of ribosomal RNA gene expression.
Molecular PsychiatryPatterns of gene expression in the limbic system of suicides with and without major depression
196 Citations2007Adolfo Sequeira, Timothy A. Klempan +5 more
The data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.
Journal of Affective DisordersCharacterization of impulsivity in suicide completers: Clinical, behavioral and psychosocial dimensions
194 Citations2006Hana Zouk, Michel Tousignant +3 more
Most of the known clinical and behavioral risk factors commonly associated with suicide are particularly valid for impulsive suicide completers, and triggering and adverse life events seem to play a role primarily inImpulsive suicide.
Molecular PsychiatryAberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins
192 Citations2007Go Kuratomi, Kazuya Iwamoto +6 more
The results suggest that altered DNA methylation statuses of PPIEL might have some significance in pathophysiology of bipolar disorder.
Proceedings of the National Academy of SciencesHistone hyperacetylation induces demethylation of reelin and 67-kDa glutamic acid decarboxylase promoters
189 Citations2007Erbo Dong, Alessandro Guidotti +2 more
Journal of Biological ChemistryThe Methyl Donor S-Adenosylmethionine Inhibits Active Demethylation of DNA
181 Citations2003Nancy Detich, Stefan Hamm +3 more
The data support an alternative mechanism of action for AdoMet as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA.
American Journal of PsychiatryAttempted suicide among living co-twins of twin suicide victims
165 Citations1995A. Roy, Nancy L. Segal +1 more
Although monozygotic and dizygotic twins may have some differing developmental experiences, these results contribute to findings of previous studies of suicide in twins in suggesting that genetic factors may play a role in suicidal behavior.
NeuroreportDNA hypermethylation of the alpha synuclein promoter in patients with alcoholism
162 Citations2005Dominikus B nsch, Bernd Lenz +2 more
A significant increase of the alpha synuclein promoter DNA methylation in patients with alcoholism which was significantly associated with their elevated homocysteine levels and may explain the reduced value of craving under alcohol drinking conditions.
Alcoholism Clinical and Experimental ResearchEpigenetic DNA Hypermethylation of the HERP Gene Promoter Induces Down‐regulation of Its mRNA Expression in Patients With Alcohol Dependence
161 Citations2006Stefan Bleich, Bernd Lenz +5 more
As hypermethylation of DNA is an important epigenetic factor in the down-regulation of gene expression, and as HERP has been considered to play an essential role within the intracellular defense system, these findings may be useful in the understanding and treatment of different disease conditions associated with alcohol dependence.
Neuroscience ResearchGene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains
156 Citations2007Mamoru Tochigi, Kazuya Iwamoto +4 more
The present results may support the hypothesis that major depression is associated with impaired cellular proliferation and plasticity, and suggest an overrepresentation of genes implicated in the downregulation or inhibition of cell proliferation.
Schizophrenia ResearchEpigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder
153 Citations2007Marin Veldić, Bashkim Kadriu +5 more
In GABAergic medium spiny neurons of CN and PT, the increased expression of DNMT1 and the decrease of reelin and GAD67 occur in SZ but not in BDP, suggesting that different epigenetic mechanisms must exist in the pathogenesis underlying SZ and BDP and implies that these disorders might involve two separate entities that are characterized by a well-defined neuropathology.
Neurochemical ResearchDecreased RNA, and Increased RNA Oxidation, in Ribosomes from Early Alzheimer’s Disease
141 Citations2006Qunxing Ding, William R. Markesbery +2 more
The amount of ribosomal RNA in the different ribosome fractions generated from control subjects, individuals with mild cognitive impairment (MCI), and individuals with AD is examined to suggest a role for RNA alterations within the ribosomes as a mediator of decreased protein synthesis in both MCI and AD.
Genome ResearchHuman ribosomal RNA gene arrays display a broad range of palindromic structures
140 Citations2005Sandrine Caburet, Chiara Conti +4 more
Findings show that rRNA genes are a mosaic of canonical and (presumably nonfunctional) palindromic units that may be altered by factors associated with genomic instability and pathology.
Bipolar DisordersSuicidal behavior: is there a genetic predisposition?
140 Citations2001Gustavo Turecki
The data that support the role of genetic factors in the predisposition to suicidal behavior are reviewed and whether or not these factors are part of the genetic liability to mood disorders are examined.
Psychological MedicineNatural history of suicidal behaviors in a population-based sample of young adults
121 Citations2007Jelena Brezo, Joel Paris +6 more
Non-fatal suicidal behaviors in adolescents and young adults are more common than suggested by cross-sectional studies and parental reports, and the dimensional model may be more useful in explaining the relationship of suicide attempts of different age of onset.
Biological PsychiatrySuicide Brain Is Associated with Decreased Expression of Neurotrophins
119 Citations2005Yogesh Dwivedi, Amal Chandra Mondal +2 more
The findings of altered expression of neurotrophins in postmortem brain of suicide victims suggest that these molecules might play a vital role in the pathophysiology of suicide.
Pharmacology & TherapeuticsNew insights into the mechanisms of antidepressant therapy
112 Citations2004Patrick D. Schloss, Fritz A. Henn
Evidence has emerged that remissions induced in patients using lithium or electroconvulsive therapy are accompanied by structural changes in neuronal networks thereby affecting synaptic plasticity in various regions of the brain.
Journal of Statistical Planning and InferenceEffect magnitude: A different focus
102 Citations2006Roger E. Kirk
Psychological MedicineLife trajectories and burden of adversity: mapping the developmental profiles of suicide mortality
99 Citations2007Monique Séguin, Alain Lesage +6 more
The life calendar approach presented here in suicide research adds to the identification of life events, distal and recent, previously associated with suicide and quantifies the burden of adversity over the life course, defining two distinct profiles that could benefit from distinct targeted preventive intervention.
Environmental Health and Preventive MedicineEpigenetics in mood disorders
81 Citations2007Patrick O. McGowan, Tadafumi Kato
Fragmentary findings suggest the possible role of epigenetics in mood disorders and the role of genomic imprinting in bipolar disorder.
Molecular and Cellular BiologyEpigenetic Programming of the rRNA Promoter by MBD3
73 Citations2007Shelley E. Brown, Moshe Szyf
It is demonstrated that this demethylation occurs following the overexpression of MBD3 and its increased interaction with the methylated rRNA promoter, the first demonstration thatMBD3 is involved in inducing and maintaining the demethylated state of a specific promoter.
Nucleic Acids ResearchThe role of acetylation in rDNA transcription
70 Citations2001Iwona Hirschler‐Laszkiewicz
The results suggest that the organization of ribosomal chromatin of higher eukaryotes is not static and that acetylation may be involved in affecting these dynamic changes directly through histone acetylations and/or through acetylated of UBF or one of the other components of rDNA transcription.
Brain ResearchCyclic AMP-mediated signaling components are upregulated in the prefrontal cortex of depressed suicide victims
63 Citations2001Y. Odagaki, Jesús A. García‐Sevilla +4 more
The results indicate that the components of cyclic AMP signaling are upregulated in a coordinated manner in brains of depressed suicides and that this alteration is not related to antidepressant treatment.
The FASEB JournalAccelerated methylation of ribosomal RNA genes during the cellular senescence of Werner syndrome fibroblasts
62 Citations2000Amrita Machwe, David K. Orren +1 more
The analysis revealed that the rDNA species observed in this study were longer, linear rDNA molecules attributable to the inhibition of EcoRI cleavage by methylation, and isoschizomeric restriction analysis confirmed that in vitro senescence of fibroblasts is accompanied by significant increases in cytosine methylation within rDNA genes.
Molecular and Cellular BiologyEpigenetic Programming of the rRNA Promoter by MBD3
60 Citations2008Shelley E. Brown, Moshe Szyf
It is demonstrated that this demethylation occurs following the overexpression of MBD3 and its increased interaction with the methylated rRNA promoter, the first demonstration thatMBD3 is involved in inducing and maintaining the demethylated state of a specific promoter.
OMICS A Journal of Integrative BiologyGenome Wide Gene Expression Studies in Mood Disorders
60 Citations2006Adolfo Sequeira, Gustavo Turecki
Despite the apparent disparate and not always concordant results, it appears evident that this technology is a powerful and inevitable approach for the study of mood disorders, especially when phenotype-specific confounders are properly accounted for.
Archives of General PsychiatryDifferential and Brain Region–Specific Regulation of Rap-1 and Epac in Depressed Suicide Victims
49 Citations2006Yogesh Dwivedi, Amal Chandra Mondal +6 more
Findings of differential regulation of Rap-1 and Epac between brain regions suggest the relevance of these molecules in the pathophysiology of depression.
Journal of Biological ChemistryRole of DNA Methyltransferases in Regulation of Human Ribosomal RNA Gene Transcription
43 Citations2006Sarmila Majumder, Kalpana Ghoshal +4 more
Humana Press eBooksNearest-Neighbor Analysis
34 Citations2003Bernard Ramsahoye
DESCRIPTION Score 0 PDCD1 PD CD1:programmed cell death 1 0 1 CCL3 4 2 4 8 0 0 .0 3 d n a g i l ) f i t o m C C ( e n i k o m e h c : 3 L C C 2 PTPN13 6 7 6 7 2 0 .
Naissance d'une population : les français établis au Canada au XVIIe siècle
34 Citations1987Hubert Charbonneau, Presses de l'université de Montréal