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Role of Epigenetic Gene Regulation in Brain Function
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Role of Epigenetic Gene Regulation in Brain Function

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (15 December 2016) | Viewed by 121365

Special Issue Editor

Prof. Dr. Dennis R. Grayson

E-Mail Website
Guest Editor
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
Interests: epigenetics of psychiatric disorders; schizophrenia; autism spectrum disorder; DNA methylation; histone methylation; chronic ethanol exposure

Special Issue Information

Dear Colleagues,

With the technological advancements in microarray platforms and in massively parallel sequencing, epigenetic studies have allowed researchers to examine epigenetic marks across the genome. The finding that 5-methylcytosine (5mC) can be further oxidized forming hydroxymethylcytosine, formylcytosine and carboxycytosine by TET protein family members has opened the doors to explorations. The ultimate removal of 5mC by enzymes of the DNA demethylation pathway has altered our appreciation and understanding of the epigenome. Nowhere has this been more apparent than in the brain. Psychiatric disorders including psychosis, anxiety, mood and addiction all have an epigenetic component. Research in the fields of neuroscience and biological psychiatry has grown in recent years and there has been a shift towards studies that will provide a better understanding of the role of epigenetic gene regulation in the etiology of psychiatric disorders. Articles in this special issue should provide insight into how epigenetic changes impact brain function by altering gene regulation (either coordinate activation/repression of selected target genes or genome-wide). For example, papers focusing on DNA methylation/demethylation both during development and in adulthood would be of interest. This includes studies of histone modifications as they play a major role in regulating gene expression in the brain.

Prof. Dr. Dennis R. Grayson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Epigenetics
  • DNA methylation
  • chromatin remodeling
  • histone modifications
  • micro RNAs
  • long non-coding RNAs
  • psychiatric disorders

Published Papers (15 papers)

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Editorial

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174 KiB  
Editorial
Special Issue Introduction: Role of Epigenetic Gene Regulation in Brain Function
by Dennis R. Grayson
Genes 2017, 8(7), 181; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8070181 - 13 Jul 2017
Cited by 2 | Viewed by 3362
Abstract
In 1957, Conrad H. Waddington published a paper in which he demonstrated the inheritance of an acquired characteristic in a population in response to an environmental stimulus [1].[...] Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)

Research

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695 KiB  
Article
DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age
by Alexey Kozlenkov, Andrew E. Jaffe, Alisa Timashpolsky, Pasha Apontes, Sergei Rudchenko, Mihaela Barbu, William Byne, Yasmin L. Hurd, Steve Horvath and Stella Dracheva
Genes 2017, 8(6), 152; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8060152 - 30 May 2017
Cited by 59 | Viewed by 7056
Abstract
We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm) in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC) of heroin users who died from heroin overdose (N = 37), suicide completers (N = 22) [...] Read more.
We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm) in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC) of heroin users who died from heroin overdose (N = 37), suicide completers (N = 22) with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28). We identified 1298 differentially methylated CpG sites (DMSs) between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0.001). DMSs and corresponding genes (DMGs) in heroin users showed significant differences in the preferential context of hyper and hypo DM. HyperDMSs were enriched in gene bodies and exons but depleted in promoters, whereas hypoDMSs were enriched in promoters and enhancers. In addition, hyperDMGs showed preference for genes expressed specifically by glutamatergic as opposed to GABAergic neurons and enrichment for axonogenesis- and synaptic-related gene ontology categories, whereas hypoDMGs were enriched for transcription factor activity- and gene expression regulation-related terms. Finally, we found that the DNAm-based “epigenetic age” of neurons from heroin users was younger than that in controls. Suicide-related results were more difficult to interpret. Collectively, these findings suggest that the observed DNAm differences could represent functionally significant marks of heroin-associated plasticity in the OFC. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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988 KiB  
Article
Variability of DNA Methylation within Schizophrenia Risk Loci across Subregions of Human Hippocampus
by W. Brad Ruzicka, Sivan Subburaju and Francine M. Benes
Genes 2017, 8(5), 143; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8050143 - 15 May 2017
Cited by 11 | Viewed by 4239
Abstract
Identification of 108 genomic regions significantly associated with schizophrenia risk by the Psychiatric Genomics Consortium was a milestone for the field, and much work is now focused on determining the mechanism of risk associated with each locus. Within these regions, we investigated variability [...] Read more.
Identification of 108 genomic regions significantly associated with schizophrenia risk by the Psychiatric Genomics Consortium was a milestone for the field, and much work is now focused on determining the mechanism of risk associated with each locus. Within these regions, we investigated variability of DNA methylation, a low-level cellular phenotype closely linked to genotype, in two highly similar cellular populations sampled from the human hippocampus, to draw inferences about the elaboration of genotype to phenotype within these loci enriched for schizophrenia risk. DNA methylation was assessed with the Illumina HumanMethylation450 BeadArray in tissue laser-microdissected from the stratum oriens of subfield CA1 or CA2/3, regions having unique connectivity with intrinsic and extrinsic fiber systems within the hippocampus. Samples consisted of postmortem human hippocampus tissue from eight schizophrenia patients, eight bipolar disorder patients, and eight healthy control subjects. Within these genomic regions, we observed far greater difference in methylation patterns between circuit locations within subjects than in a single subregion between subjects across diagnostic groups, demonstrating the complexity of genotype to phenotype elaboration across the diverse circuitry of the human brain. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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2184 KiB  
Article
Neurotoxic Doses of Chronic Methamphetamine  Trigger Retrotransposition of the Identifier Element  in Rat Dorsal Dentate Gyrus
by Anna Moszczynska, Kyle J. Burghardt and Dongyue Yu
Genes 2017, 8(3), 96; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8030096 - 06 Mar 2017
Cited by 4 | Viewed by 5638
Abstract
Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present investigation was [...] Read more.
Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present investigation was to determine whether neurotoxic doses of binge or chronic methamphetamine (METH) trigger retrotransposition of the identifier (ID) element, a member of the rat SINE family, in the dentate gyrus genomic DNA. Adult male Sprague‐Dawley rats were treated with saline or high doses of binge or chronic METH and sacrificed at three different time points thereafter. DNA methylation analysis, immunohistochemistry and next‐generation sequencing (NGS) were performed on the dorsal dentate gyrus samples. Binge METH triggered hypomethylation, while chronic METH triggered hypermethylation of the CpG‐2 site. Both METH regimens were associated with increased intensities in poly(A)‐binding protein 1 (PABP1, a SINE regulatory protein)‐like immunohistochemical staining in the dentate gyrus. The amplification of several ID element sequences was significantly higher in the chronic METH group than in the control group a week after METH, and they mapped to genes coding for proteins regulating cell growth and proliferation, transcription, protein function as well as for a variety of transporters. The results suggest that chronic METH induces ID element retrotransposition in the dorsal dentate gyrus and may affect hippocampal neurogenesis. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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2156 KiB  
Article
The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice
by Sabine A. S. Langie, Kerry M. Cameron, Gabriella Ficz, David Oxley, Bartłomiej Tomaszewski, Joanna P. Gorniak, Lou M. Maas, Roger W. L. Godschalk, Frederik J. Van Schooten, Wolf Reik, Thomas Von Zglinicki and John C. Mathers
Genes 2017, 8(2), 75; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8020075 - 17 Feb 2017
Cited by 21 | Viewed by 8232
Abstract
Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of [...] Read more.
Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events (e.g., DNA methylation) contribute to the ageing process and may be functionally important through the regulation of the expression of DNA repair genes. We hypothesize that epigenetic mechanisms are involved in mediating the age-related decline in BER in the brain. Brains from male mice were isolated at 3–32 months of age. Pyrosequencing analyses revealed significantly increased Ogg1 methylation with ageing, which correlated inversely with Ogg1 expression. The reduced Ogg1 expression correlated with enhanced expression of methyl-CpG binding protein 2 and ten-eleven translocation enzyme 2. A significant inverse correlation between Neil1 methylation at CpG-site2 and expression was also observed. BER activity was significantly reduced and associated with increased 8-oxo-7,8-dihydro-2′-deoxyguanosine levels. These data indicate that Ogg1 and Neil1 expression can be epigenetically regulated, which may mediate the effects of ageing on DNA repair in the brain. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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2050 KiB  
Article
mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain
by Sern-Yih Cheah, Bruce R. Lawford, Ross McD. Young, Charles P. Morris and Joanne Voisey
Genes 2017, 8(1), 14; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8010014 - 04 Jan 2017
Cited by 33 | Viewed by 6514
Abstract
Serotonin receptor 2A (HTR2A) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance of HTR2A in schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have [...] Read more.
Serotonin receptor 2A (HTR2A) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance of HTR2A in schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have reported inconsistent results. In this study, we examine HTR2A expression and methylation and the interaction with HTR2A polymorphisms to identify their biological significance in schizophrenia. Subjects included 25 schizophrenia and 25 control post-mortem brain samples. Genotype and mRNA data was generated by transcriptome sequencing. DNA methylation profiles were generated for CpG sites within promoter-exon I region. Expression, genotype and methylation data were examined for association with schizophrenia. HTR2A mRNA levels were reduced by 14% (p = 0.006) in schizophrenia compared to controls. Three CpG sites were hypermethylated in schizophrenia (cg5 p = 0.028, cg7 p = 0.021, cg10 p = 0.017) and HTR2A polymorphisms rs6314 (p = 0.008) and rs6313 (p = 0.026) showed genetic association with schizophrenia. Differential DNA methylation was associated with rs6314 and rs6313. There was a strong correlation between HTR2A DNA methylation and mRNA expression. The results were nominally significant but did not survive the rigorous Benjamini-Hochberg correction for multiple testing. Differential HTR2A expression in schizophrenia in our study may be the result of the combined effect of multiple differentially methylated CpG sites. Epigenetic HTR2A regulation may alter brain function, which contributes to the development of schizophrenia. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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Review

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1071 KiB  
Review
Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring
by Avijit Banik, Deepika Kandilya, Seshadri Ramya, Walter Stünkel, Yap Seng Chong and S. Thameem Dheen
Genes 2017, 8(6), 150; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8060150 - 24 May 2017
Cited by 90 | Viewed by 15573
Abstract
It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such [...] Read more.
It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down’s syndrome, Rett syndrome, and later onset of neuropsychological deficits. This review comprehensively describes the recent findings in the epigenetic landscape contributing to altered molecular profiles resulting in NDs. Furthermore, we will discuss potential avenues for future research to identify diagnostic markers and therapeutic epi-drugs to reverse these abnormalities in the brain as epigenetic marks are plastic and reversible in nature. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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1048 KiB  
Review
CpG and Non-CpG Methylation in Epigenetic Gene Regulation and Brain Function
by Hyun Sik Jang, Woo Jung Shin, Jeong Eon Lee and Jeong Tae Do
Genes 2017, 8(6), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8060148 - 23 May 2017
Cited by 257 | Viewed by 21226
Abstract
DNA methylation is a major epigenetic mark with important roles in genetic regulation. Methylated cytosines are found primarily at CpG dinucleotides, but are also found at non-CpG sites (CpA, CpT, and CpC). The general functions of CpG and non-CpG methylation include gene silencing [...] Read more.
DNA methylation is a major epigenetic mark with important roles in genetic regulation. Methylated cytosines are found primarily at CpG dinucleotides, but are also found at non-CpG sites (CpA, CpT, and CpC). The general functions of CpG and non-CpG methylation include gene silencing or activation depending on the methylated regions. CpG and non-CpG methylation are found throughout the whole genome, including repetitive sequences, enhancers, promoters, and gene bodies. Interestingly, however, non-CpG methylation is restricted to specific cell types, such as pluripotent stem cells, oocytes, neurons, and glial cells. Thus, accumulation of methylation at non-CpG sites and CpG sites in neurons seems to be involved in development and disease etiology. Here, we provide an overview of CpG and non-CpG methylation and their roles in neurological diseases. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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1277 KiB  
Review
Epigenetic Regulation of Telomere Maintenance for Therapeutic Interventions in Gliomas
by Elisabeth Naderlinger and Klaus Holzmann
Genes 2017, 8(5), 145; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8050145 - 17 May 2017
Cited by 22 | Viewed by 6439
Abstract
High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a common human brain tumor with poor patient outcome. Astrocytoma demonstrates two known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA) and on alternative lengthening of telomeres (ALT). ALT is associated [...] Read more.
High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a common human brain tumor with poor patient outcome. Astrocytoma demonstrates two known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA) and on alternative lengthening of telomeres (ALT). ALT is associated with lower tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors by direct mutation and epigenetic activation of the hTERT promoter is well established. Here, we summarize the genetic background of TMMs in non-malignant cells and in cancer, in addition to clinical and pathological features of gliomas. Furthermore, we present new evidence for epigenetic mechanisms (EMs) involved in regulation of ALT and TA with special emphasis on human diffuse gliomas as potential therapeutic drug targets. We discuss the role of TMM associated telomeric chromatin factors such as DNA and histone modifying enzymes and non-coding RNAs including microRNAs and long telomeric TERRA transcripts. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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274 KiB  
Review
The Crucial Role of DNA Methylation and MeCP2 in Neuronal Function
by Maria Fasolino and Zhaolan Zhou
Genes 2017, 8(5), 141; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8050141 - 13 May 2017
Cited by 57 | Viewed by 6662
Abstract
A neuron is unique in its ability to dynamically modify its transcriptional output in response to synaptic activity while maintaining a core gene expression program that preserves cellular identity throughout a lifetime that is longer than almost every other cell type in the [...] Read more.
A neuron is unique in its ability to dynamically modify its transcriptional output in response to synaptic activity while maintaining a core gene expression program that preserves cellular identity throughout a lifetime that is longer than almost every other cell type in the body. A contributing factor to the immense adaptability of a neuron is its unique epigenetic landscape that elicits locus-specific alterations in chromatin architecture, which in turn influences gene expression. One such epigenetic modification that is sensitive to changes in synaptic activity, as well as essential for maintaining cellular identity, is DNA methylation. The focus of this article is on the importance of DNA methylation in neuronal function, summarizing recent studies on critical players in the establishment of (the “writing”), the modification or erasure of (the “editing”), and the mediation of (the “reading”) DNA methylation in neurodevelopment and neuroplasticity. One “reader” of DNA methylation in particular, methyl-CpG-binding protein 2 (MeCP2), is highlighted, given its undisputed importance in neuronal function. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
1011 KiB  
Review
DNA Methylation Dynamics and Cocaine in the Brain: Progress and Prospects
by Kathryn Vaillancourt, Carl Ernst, Deborah Mash and Gustavo Turecki
Genes 2017, 8(5), 138; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8050138 - 12 May 2017
Cited by 34 | Viewed by 6208
Abstract
Cytosine modifications, including DNA methylation, are stable epigenetic marks that may translate environmental change into transcriptional regulation. Research has begun to investigate DNA methylation dynamics in relation to cocaine use disorders. Specifically, DNA methylation machinery, including methyltransferases and binding proteins, are dysregulated in [...] Read more.
Cytosine modifications, including DNA methylation, are stable epigenetic marks that may translate environmental change into transcriptional regulation. Research has begun to investigate DNA methylation dynamics in relation to cocaine use disorders. Specifically, DNA methylation machinery, including methyltransferases and binding proteins, are dysregulated in brain reward pathways after chronic cocaine exposure. In addition, numerous methylome-wide and candidate promoter studies have identified differential methylation, at the nucleotide level, in rodent models of cocaine abuse and drug seeking behavior. This review highlights the current progress in the field of cocaine-related methylation, and offers considerations for future research. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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1340 KiB  
Review
Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure
by David P. Gavin, Dennis R. Grayson, Sajoy P. Varghese and Marina Guizzetti
Genes 2017, 8(5), 137; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8050137 - 11 May 2017
Cited by 14 | Viewed by 6425
Abstract
Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. [...] Read more.
Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced differentiation changes with developmental alterations in chromatin structure remain to be elucidated. In the first part of this review, we discuss the sequence of chromatin structural changes involved in neural cell differentiation during normal development. We then discuss the effects of prenatal alcohol on developmental histone modifications and DNA methylation in the context of neurogenesis and astrogliogenesis. We attempt to synthesize the developmental literature with the FASD literature, proposing that alcohol-induced changes to chromatin structure account for altered neurogenesis and astrogliogenesis as well as altered neuron and astrocyte differentiation. Together these changes may contribute to the cognitive and behavioral abnormalities in FASD. Future studies using standardized alcohol exposure paradigms at specific developmental stages will advance the understanding of how chromatin structural changes impact neural cell fate and maturation in FASD. Full article
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662 KiB  
Review
The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders
by Marija Kundakovic and Ivana Jaric
Genes 2017, 8(3), 104; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8030104 - 18 Mar 2017
Cited by 127 | Viewed by 12500
Abstract
Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and [...] Read more.
Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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209 KiB  
Review
Epigenetics in Stroke Recovery
by Haifa Kassis, Amjad Shehadah, Michael Chopp and Zheng Gang Zhang
Genes 2017, 8(3), 89; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8030089 - 27 Feb 2017
Cited by 29 | Viewed by 4970
Abstract
Abstract: While the death rate from stroke has continually decreased due to interventions in the hyperacute stage of the disease, long-term disability and institutionalization have become common sequelae in the aftermath of stroke. Therefore, identification of new molecular pathways that could be targeted [...] Read more.
Abstract: While the death rate from stroke has continually decreased due to interventions in the hyperacute stage of the disease, long-term disability and institutionalization have become common sequelae in the aftermath of stroke. Therefore, identification of new molecular pathways that could be targeted to improve neurological recovery among survivors of stroke is crucial. Epigenetic mechanisms such as post-translational modifications of histone proteins and microRNAs have recently emerged as key regulators of the enhanced plasticity observed during repair processes after stroke. In this review, we highlight the recent advancements in the evolving field of epigenetics in stroke recovery. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
754 KiB  
Review
Primetime for Learning Genes
by Joyce Keifer
Genes 2017, 8(2), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8020069 - 11 Feb 2017
Cited by 9 | Viewed by 5401
Abstract
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among [...] Read more.
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli. Full article
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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