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Migliore L, Coppedè F. Gene-environment interactions in Alzheimer disease: the emerging role of epigenetics. Nat Rev Neurol 2022; 18:643-660. [PMID: 36180553 DOI: 10.1038/s41582-022-00714-w] [Citation(s) in RCA: 93] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2022] [Indexed: 12/15/2022]
Abstract
With the exception of a few monogenic forms, Alzheimer disease (AD) has a complex aetiology that is likely to involve multiple susceptibility genes and environmental factors. The role of environmental factors is difficult to determine and, until a few years ago, the molecular mechanisms underlying gene-environment (G × E) interactions in AD were largely unknown. Here, we review evidence that has emerged over the past two decades to explain how environmental factors, such as diet, lifestyle, alcohol, smoking and pollutants, might interact with the human genome. In particular, we discuss how various environmental AD risk factors can induce epigenetic modifications of key AD-related genes and pathways and consider how epigenetic mechanisms could contribute to the effects of oxidative stress on AD onset. Studies on early-life exposures are helping to uncover critical time windows of sensitivity to epigenetic influences from environmental factors, thereby laying the foundations for future primary preventative approaches. We conclude that epigenetic modifications need to be considered when assessing G × E interactions in AD.
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Affiliation(s)
- Lucia Migliore
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy. .,Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy.
| | - Fabio Coppedè
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy
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DNA Methylation and Type 2 Diabetes: Novel Biomarkers for Risk Assessment? Int J Mol Sci 2021; 22:ijms222111652. [PMID: 34769081 PMCID: PMC8584054 DOI: 10.3390/ijms222111652] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/25/2021] [Accepted: 10/25/2021] [Indexed: 12/15/2022] Open
Abstract
Diabetes is a severe threat to global health. Almost 500 million people live with diabetes worldwide. Most of them have type 2 diabetes (T2D). T2D patients are at risk of developing severe and life-threatening complications, leading to an increased need for medical care and reduced quality of life. Improved care for people with T2D is essential. Actions aiming at identifying undiagnosed diabetes and at preventing diabetes in those at high risk are needed as well. To this end, biomarker discovery and validation of risk assessment for T2D are critical. Alterations of DNA methylation have recently helped to better understand T2D pathophysiology by explaining differences among endophenotypes of diabetic patients in tissues. Recent evidence further suggests that variations of DNA methylation might contribute to the risk of T2D even more significantly than genetic variability and might represent a valuable tool to predict T2D risk. In this review, we focus on recent information on the contribution of DNA methylation to the risk and the pathogenesis of T2D. We discuss the limitations of these studies and provide evidence supporting the potential for clinical application of DNA methylation marks to predict the risk and progression of T2D.
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The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review. Int J Mol Sci 2020; 21:ijms21030826. [PMID: 32012861 PMCID: PMC7037192 DOI: 10.3390/ijms21030826] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 01/25/2020] [Accepted: 01/26/2020] [Indexed: 01/31/2023] Open
Abstract
Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD’s etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (BDNF, MAOA, SLC6A2, SLC6A4, HTR1A, HTR1B, IL6, IL11) and whole genome methylation. Methylation of certain sites within BDNF, SLC6A4, HTR1A, HTR1B, IL11, and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals’ unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.
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Roy B, Dwivedi Y. Understanding the Neuroepigenetic Constituents of Suicide Brain. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2018; 157:233-262. [PMID: 29933952 DOI: 10.1016/bs.pmbts.2018.01.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Stressful life incidents often cause a predisposition for developing mental disorders such as major depressive disorder (MDD). Impaired neurocognitive and neuro-vegetative functions of the central nervous system are the hallmarks of this mental illness. Blunted responses from emotionally salient regions of the brain including cortex, hippocampus, and amygdala have been associated with MDD-related behavioral changes. Moreover, improper signal processing and neuronal atrophy were held responsible for the overall dysfunctionality of these vulnerable regions in the MDD brain. The prevalence of genetic susceptibility along with adverse environmental stimuli often makes the situation worse for MDD patients, leading to an increased risk of suicidal behavior and eventually death by suicide. Despite considerable efforts to understand the complex neurobiology associated with MDD and suicidal behavior, their pathological determinants remain mostly elusive. Recent research, however, has shown that epigenetic perturbations have a formidable impact on the etiopathogenesis of MDD. Understanding the neuroepigenetic nature of this mental disorder may provide opportunities to devise more effective treatment strategies. Moreover, this can potentially lead to identifying predictive biomarkers associated with suicide risk. The present chapter critically reviews studies pertaining to epigenetic signatures of MDD and suicide brain.
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Affiliation(s)
- Bhaskar Roy
- University of Alabama at Birmingham, Birmingham, AL, United States
| | - Yogesh Dwivedi
- University of Alabama at Birmingham, Birmingham, AL, United States.
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Understanding epigenetic architecture of suicide neurobiology: A critical perspective. Neurosci Biobehav Rev 2016; 72:10-27. [PMID: 27836463 DOI: 10.1016/j.neubiorev.2016.10.031] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 09/26/2016] [Accepted: 10/31/2016] [Indexed: 12/29/2022]
Abstract
Current understanding of environmental cross-talk with genetic makeup is found to be mediated through an epigenetic interface which is associated with prominent reversible and heritable changes at gene expression level. Recent emergence of epigenetic modulation in shaping the genetic information has become a key regulatory factor in answering the underlying complexities associated with several mental disorders. A comprehensive understanding of the pertinent changes in the epigenetic makeup of suicide phenotype exhibits a characteristic signature with the possibility of using it as a biomarker to help predict the risk factors associated with suicide. Within the scope of this current review, the most sought after epigenetic changes of DNA methylation and histone modification are thoroughly scrutinized to understand their close functional association with the broad spectrum of suicide phenotype.
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Sharma RP, Feiner B, Chase KA. Histone H3 phosphorylation is upregulated in PBMCs of schizophrenia patients in comparison to healthy controls. Schizophr Res 2015; 169:498-499. [PMID: 26476617 PMCID: PMC4835025 DOI: 10.1016/j.schres.2015.09.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 09/24/2015] [Accepted: 09/27/2015] [Indexed: 10/22/2022]
Affiliation(s)
- Rajiv P. Sharma
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, United States. Jesse Brown Veterans Affairs Medical Center, 820 South Damen Avenue (M/C 151), Chicago, IL 60612, United States
| | - Benjamin Feiner
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, United States
| | - Kayla A. Chase
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, United States
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Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nat Rev Genet 2015; 16:641-52. [PMID: 26416311 DOI: 10.1038/nrg3964] [Citation(s) in RCA: 197] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Behavioural traits in mammals are influenced by environmental factors, which can interact with the genome and modulate its activity by complex molecular interplay. Environmental experiences can modify social, emotional and cognitive behaviours during an individual's lifetime, and result in acquired behavioural traits that can be transmitted to subsequent generations. This Review discusses the concept of, and experimental support for, non-genetic transgenerational inheritance of acquired traits involving the germ line in mammals. Possible mechanisms of induction and maintenance during development and adulthood are considered along with an interpretation of recent findings showing the involvement of epigenetic modifications and non-coding RNAs in male germ cells.
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Lardenoije R, Iatrou A, Kenis G, Kompotis K, Steinbusch HWM, Mastroeni D, Coleman P, Lemere CA, Hof PR, van den Hove DLA, Rutten BPF. The epigenetics of aging and neurodegeneration. Prog Neurobiol 2015; 131:21-64. [PMID: 26072273 PMCID: PMC6477921 DOI: 10.1016/j.pneurobio.2015.05.002] [Citation(s) in RCA: 246] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Revised: 05/13/2015] [Accepted: 05/13/2015] [Indexed: 12/14/2022]
Abstract
Epigenetics is a quickly growing field encompassing mechanisms regulating gene expression that do not involve changes in the genotype. Epigenetics is of increasing relevance to neuroscience, with epigenetic mechanisms being implicated in brain development and neuronal differentiation, as well as in more dynamic processes related to cognition. Epigenetic regulation covers multiple levels of gene expression; from direct modifications of the DNA and histone tails, regulating the level of transcription, to interactions with messenger RNAs, regulating the level of translation. Importantly, epigenetic dysregulation currently garners much attention as a pivotal player in aging and age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, where it may mediate interactions between genetic and environmental risk factors, or directly interact with disease-specific pathological factors. We review current knowledge about the major epigenetic mechanisms, including DNA methylation and DNA demethylation, chromatin remodeling and non-coding RNAs, as well as the involvement of these mechanisms in normal aging and in the pathophysiology of the most common neurodegenerative diseases. Additionally, we examine the current state of epigenetics-based therapeutic strategies for these diseases, which either aim to restore the epigenetic homeostasis or skew it to a favorable direction to counter disease pathology. Finally, methodological challenges of epigenetic investigations and future perspectives are discussed.
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Affiliation(s)
- Roy Lardenoije
- School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands
| | - Artemis Iatrou
- School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands
| | - Gunter Kenis
- School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands
| | - Konstantinos Kompotis
- Center for Integrative Genomics, University of Lausanne, Genopode Building, 1015 Lausanne-Dorigny, Switzerland
| | - Harry W M Steinbusch
- School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands
| | - Diego Mastroeni
- School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands; L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA
| | - Paul Coleman
- L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA
| | - Cynthia A Lemere
- Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
| | - Patrick R Hof
- Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
| | - Daniel L A van den Hove
- School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands; Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany
| | - Bart P F Rutten
- School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
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Balan S, Iwayama Y, Maekawa M, Toyota T, Ohnishi T, Toyoshima M, Shimamoto C, Esaki K, Yamada K, Iwata Y, Suzuki K, Ide M, Ota M, Fukuchi S, Tsujii M, Mori N, Shinkai Y, Yoshikawa T. Exon resequencing of H3K9 methyltransferase complex genes, EHMT1, EHTM2 and WIZ, in Japanese autism subjects. Mol Autism 2014; 5:49. [PMID: 25400900 PMCID: PMC4233047 DOI: 10.1186/2040-2392-5-49] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Accepted: 09/23/2014] [Indexed: 12/21/2022] Open
Abstract
Background Histone H3 methylation at lysine 9 (H3K9) is a conserved epigenetic signal, mediating heterochromatin formation by trimethylation, and transcriptional silencing by dimethylation. Defective GLP (Ehmt1) and G9a (Ehmt2) histone lysine methyltransferases, involved in mono and dimethylation of H3K9, confer autistic phenotypes and behavioral abnormalities in animal models. Moreover, EHMT1 loss of function results in Kleefstra syndrome, characterized by severe intellectual disability, developmental delays and psychiatric disorders. We examined the possible role of histone methyltransferases in the etiology of autism spectrum disorders (ASD) and suggest that rare functional variants in these genes that regulate H3K9 methylation may be associated with ASD. Methods Since G9a-GLP-Wiz forms a heteromeric methyltransferase complex, all the protein-coding regions and exon/intron boundaries of EHMT1, EHMT2 and WIZ were sequenced in Japanese ASD subjects. The detected variants were prioritized based on novelty and functionality. The expression levels of these genes were tested in blood cells and postmortem brain samples from ASD and control subjects. Expression of EHMT1 and EHMT2 isoforms were determined by digital PCR. Results We identified six nonsynonymous variants: three in EHMT1, two in EHMT2 and one in WIZ. Two variants, the EHMT1 ankyrin repeat domain (Lys968Arg) and EHMT2 SET domain (Thr961Ile) variants were present exclusively in cases, but showed no statistically significant association with ASD. The EHMT2 transcript expression was significantly elevated in the peripheral blood cells of ASD when compared with control samples; but not for EHMT1 and WIZ. Gene expression levels of EHMT1, EHMT2 and WIZ in Brodmann area (BA) 9, BA21, BA40 and the dorsal raphe nucleus (DoRN) regions from postmortem brain samples showed no significant changes between ASD and control subjects. Nor did expression levels of EHMT1 and EHMT2 isoforms in the prefrontal cortex differ significantly between ASD and control groups. Conclusions We identified two novel rare missense variants in the EHMT1 and EHMT2 genes of ASD patients. We surmise that these variants alone may not be sufficient to exert a significant effect on ASD pathogenesis. The elevated expression of EHMT2 in the peripheral blood cells may support the notion of a restrictive chromatin state in ASD, similar to schizophrenia. Electronic supplementary material The online version of this article (doi:10.1186/2040-2392-5-49) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shabeesh Balan
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Yoshimi Iwayama
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Motoko Maekawa
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Tomoko Toyota
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Tetsuo Ohnishi
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Manabu Toyoshima
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Chie Shimamoto
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Kayoko Esaki
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Kazuo Yamada
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan
| | - Yasuhide Iwata
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Katsuaki Suzuki
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Masayuki Ide
- Department of Psychiatry, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Motonori Ota
- Graduate School of Information Science, Nagoya University, Nagoya, Aichi, Japan
| | - Satoshi Fukuchi
- Faculty of Engineering, Maebashi Institute of Technology, Maebashi, Japan
| | - Masatsugu Tsujii
- Faculty of Sociology, Chukyo University, Chukyo, Aichi, Japan ; Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Norio Mori
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan ; Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Yoichi Shinkai
- Cellular Memory Laboratory, RIKEN, Wako, Saitama, Japan ; CREST (Core Research for Evolutionary Science and Technology), Japan Science and Technology Agency, Kawaguchi, Saitama, Japan
| | - Takeo Yoshikawa
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan ; CREST (Core Research for Evolutionary Science and Technology), Japan Science and Technology Agency, Kawaguchi, Saitama, Japan
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Gavin DP, Floreani C. Epigenetics of schizophrenia: an open and shut case. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2014; 115:155-201. [PMID: 25131545 DOI: 10.1016/b978-0-12-801311-3.00005-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
During the last decade and a half, there has been an explosion of data regarding epigenetic changes in schizophrenia. Most initial studies have suggested that schizophrenia is characterized by an overly restrictive chromatin state based on increases in transcription silencing histone modifications and DNA methylation at schizophrenia candidate gene promoters and increases in the expression of enzymes that catalyze their formation. However, recent studies indicate that the pathology is more complex. This complexity may greatly impact pharmacological approaches directed at targeting epigenetic abnormalities in schizophrenia. The current review explores epigenetic studies of schizophrenia and what this can tell us about the underlying pathophysiology. We hypothesize based on recent studies that it is also plausible that drugs that further restrict chromatin may be efficacious.
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Affiliation(s)
- David P Gavin
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
| | - Christina Floreani
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
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Chase KA, Gavin DP, Guidotti A, Sharma RP. Histone methylation at H3K9: evidence for a restrictive epigenome in schizophrenia. Schizophr Res 2013; 149:15-20. [PMID: 23815974 PMCID: PMC3779891 DOI: 10.1016/j.schres.2013.06.021] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2013] [Revised: 05/17/2013] [Accepted: 06/04/2013] [Indexed: 10/26/2022]
Abstract
OBJECTIVE Epigenetic changes are stable and long-lasting chromatin modifications that regulate genomewide and local gene activity. The addition of two methyl groups to the 9th lysine of histone 3 (H3K9me2) by histone methyltransferases (HMT) leads to a restrictive chromatin state, and thus reduced levels of gene transcription. Given the numerous reports of transcriptional down-regulation of candidate genes in schizophrenia, we tested the hypothesis that this illness can be characterized by a restrictive epigenome. METHODS We obtained parietal cortical samples from the Stanley Foundation Neuropathology Consortium and lymphocyte samples from the University of Illinois at Chicago (UIC). In both tissues we measured mRNA expression of HMTs GLP, SETDB1 and G9a via real-time RT-PCR and H3K9me2 levels via western blot. Clinical rating scales were obtained from the UIC cohort. RESULTS A diagnosis of schizophrenia is a significant predictor for increased GLP, SETDB1 mRNA expression and H3K9me2 levels in both postmortem brain and lymphocyte samples. G9a mRNA is significantly increased in the UIC lymphocyte samples as well. Increased HMT mRNA expression is associated with worsening of specific symptoms, longer durations of illness and a family history of schizophrenia. CONCLUSIONS These data support the hypothesis of a restrictive epigenome in schizophrenia, and may associate with symptoms that are notoriously treatment resistant. The histone methyltransferases measured here are potential future therapeutic targets for small molecule pharmacology, and better patient prognosis.
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Affiliation(s)
- Kayla A. Chase
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612
| | - David P. Gavin
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612
| | - Alessandro Guidotti
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612
| | - Rajiv P. Sharma
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612,Corresponding author: Rajiv P. Sharma MD, Professor, Psychiatric Institute, 1601 West Taylor Street, Chicago, IL 60612, Tel.: (312) 413-4508; Fax: (312) 413-4503.
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