Epigenetic Mechanisms in Cognition

Day, Jeremy J.; Sweatt, J. David

doi:10.1016/j.neuron.2011.05.019

Cited by 434 publications

(320 citation statements)

References 172 publications

(286 reference statements)

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“…During normal brain development, the connections between neurons and neuronal circuitry undergo remodeling in response to environmental cues. An emerging view is that environmental factors can also contribute to disruptions in synaptic signaling and neuronal survival (Day and Sweatt, 2011). Thus, epigenetic modifications such as methylation of DNA and histones are associated not only with learning and memory, but also with deficits in memory arising as a consequence of ischemic stroke or seizures.…”

Section: Epigenetic Modificatonsmentioning

confidence: 99%

“…Properly established and maintained patterns of DNA methylation are essential for normal brain development, lineage commitment, and normal functioning of the adult organism (Robertson, 2005;Guibert et al, 2009;Senner, 2011). DNA methylation provides stable indexing marks that extend over long chromosomal domains, giving rise to 'memorized' states of gene expression that may be inherited from one cell generation to the next (Borrelli et al, 2008;Day and Sweatt, 2011). Methylation of mammalian DNA is catalyzed by DNA methyltransferases (DNMTs), chromatin-modifying proteins that establish and maintain unique DNA methylation patterns in different cells in different contexts.…”

Section: Dna Methylationmentioning

confidence: 99%

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Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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Epigenetic remodeling and modifications of chromatin structure by DNA methylation and histone modifications represent central mechanisms for the regulation of neuronal gene expression during brain development, higher-order processing, and memory formation. Emerging evidence implicates epigenetic modifications not only in normal brain function, but also in neuropsychiatric disorders. This review focuses on recent findings that disruption of chromatin modifications have a major role in the neurodegeneration associated with ischemic stroke and epilepsy. Although these disorders differ in their underlying causes and pathophysiology, they share a common feature, in that each disorder activates the gene silencing transcription factor REST (repressor element 1 silencing transcription factor), which orchestrates epigenetic remodeling of a subset of 'transcriptionally responsive targets' implicated in neuronal death. Although ischemic insults activate REST in selectively vulnerable neurons in the hippocampal CA1, seizures activate REST in CA3 neurons destined to die. Profiling the array of genes that are epigenetically dysregulated in response to neuronal insults is likely to advance our understanding of the mechanisms underlying the pathophysiology of these disorders and may lead to the identification of novel therapeutic strategies for the amelioration of these serious human conditions.

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Section: Epigenetic Modificatonsmentioning

confidence: 99%

Section: Dna Methylationmentioning

confidence: 99%

Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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“…A common theme of these disorders is that mutations in epigenetic regulators can alter chromatin structure and induce a broad spectrum of neurological and behavioral deficits. Furthermore, environmentally induced alterations in chromatin structure in the absence of mutations have been shown to be critically important for a variety of neuronal functions, including those related to synaptic activity, cognition, and reward (Day and Sweatt, 2011;Robison and Nestler, 2011;West and Greenberg, 2011). In this review, we will attempt to describe the general principals of chromatin regulation as they relate to histone biology (ie, chemical modifications, chromatin remodeling, and histone variant exchange), with specific emphasis on the role that such processes may have in guiding various aspects of neural plasticity (Figure 1, left panel).…”

Section: Chromatin Overviewmentioning

confidence: 99%

Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity

Maze

Noh

Allis

2012

Neuropsychopharmacol

114

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Postmitotic neurons are subject to a vast array of environmental influences that require the nuclear integration of intracellular signaling events to promote a wide variety of neuroplastic states associated with synaptic function, circuit formation, and behavioral memory. Over the last decade, much attention has been paid to the roles of transcription and chromatin regulation in guiding fundamental aspects of neuronal function. A great deal of this work has centered on neurodevelopmental and adulthood plasticity, with increased focus in the areas of neuropharmacology and molecular psychiatry. Here, we attempt to provide a broad overview of chromatin regulation, as it relates to central nervous system (CNS) function, with specific emphasis on the modes of histone posttranslational modifications, chromatin remodeling, and histone variant exchange. Understanding the functions of chromatin in the context of the CNS will aid in the future development of pharmacological therapeutics aimed at alleviating devastating neurological disorders.

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“…In general, very little is known about the full extent of transcriptional regulation that is required for memory formation, or about CREB-independent mechanisms in LTM. It is clear, however, that diverse forms of epigenetic regulation are essential in this process (9,10) (Figure 1). This review highlights work performed in model organisms over the last decade that makes significant progress in uncovering the role of epigenetic regulators and chromatin modifications in various types of learning and memory.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of memory: implications in human cognitive disorders

Kramer

2013

BioMolecular Concepts

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Epigenetic modification of chromatin structure is an important mechanism in the regulation of gene expression. Recent studies have shown that dynamic regulation of chromatin structure occurs in response to neuronal stimulation associated with learning and memory. Learning-induced chromatin modifications include DNA methylation, histone acetylation, histone phosphorylation and histone methylation. Studies in animal models have used genetic and pharmacological methods to manipulate the epigenetic machinery in the brain during learning and memory formation. In general, these studies suggest that epigenetic regulation of chromatin structure is essential for long term memory (LTM) consolidation, which is known to require new gene transcription. Analysis of animal models has also implicated epigenetic mechanisms in impaired cognition associated with aging, neurodegenerative disease, and intellectual disability (ID). Recently, it has been shown that a subset of ID disorders and autism are caused by disruption of specific chromatin modification complexes that are involved in nuclear hormone receptor mediated transcriptional regulation. This review provides an overview of chromatin modifications that are implicated in learning and memory and discusses the role of chromatin modifying proteins in learning-induced transcriptional regulation and human cognitive disorders.

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Epigenetic Mechanisms in Cognition

Cited by 434 publications

References 172 publications

Epigenetic Mechanisms in Stroke and Epilepsy

Epigenetic Mechanisms in Stroke and Epilepsy

Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity

Epigenetic regulation of memory: implications in human cognitive disorders

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