Epigenetic codes in cognition and behaviour.
TL;DR: Recent findings on the role and mechanisms of epigenetic codes in the brain are described, and their implication in synaptic plasticity, cognitive functions and psychiatric disorders are discussed.
About: This article is published in Behavioural Brain Research.The article was published on 2008-09-01. It has received 260 citations till now. The article focuses on the topics: Epigenetic code & Epigenetics.
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TL;DR: In this article , the effects of male harassment in two generations of damselflies (Odonata) were analyzed in the presence of different sex-ratio and density (balanced and male-biased) to modify the male harassment level.
Abstract: Abstract Population structure determines individuals’ interactions and trade-offs with evolutionary consequences. Male-biased populations increase intrasexual competition and intersexual harassment, reducing female resource acquisition, and thus, resources availability for the following generation. We analyzed direct and cross-generational effects of male harassment in two generations of damselflies (Odonata). We exposed adult females to treatments with different sex-ratio and density (balanced and male-biased) to modify the male harassment level. We analyzed female fecundity, fertility, and number of faecal deposits as an indirect measure of resources acquisition. We studied female flight performance after repeated exposures to males. We analyzed survivorship, development, exploration, thigmotaxis, and feeding latency of larvae produced by the experimental females. In both generations, we analyzed four metrics of behavior: mean value, interindividual differences in plasticity, intra-individual unpredictability, and repeatability. Mating duration increased in male-biased treatment, whereas female resources acquisition and fertility decreased. Females that mated longer showed higher fecundity when they were exposed to balanced treatment, but not if they were exposed to male-biased treatment. Females from the male-biased treatment showed interindividual differences in plasticity and no repeatability in flight performance. Offspring showed balanced sex-ratio and similar survivorship, development, and feeding latency independently of the parental treatment; however, females exposed to male-biased treatment produced offspring with higher differences in exploration plasticity and daughters less explorative and with higher unpredictable thigmotaxis. We propose prolonged copulation as courtship at balanced sex-ratio but a cost to females under male-biased sex-ratio. Cross-generational effects in behavioral variability may be a mechanism to cope with predicted future environments.
2 citations
Dissertation•
08 Apr 2013
TL;DR: This work is original in that it is the first to report on a role of one member of this family in oocyte meiosis and paternal chromatin assembly in the zygote and identifies Yemanuclein as a partner of HIRA in its role in H3.3 nucleosome assembly and deposition on the paternal pronucleus.
Abstract: Sexual reproduction relies on two key events: formation of cells with a haploid genome through meiosis and restoration of diploidy through syngamy in the zygote. Meiosis completion is supported exclusively by the maternal genome for the oocyte and the paternal genome for the sperm cell. In contrast diploidy restoration in the zygote is entirely dependent on maternal factors. At the end of meiosis the maternal pronucleus is competent for replication, whereas the paternal genome is packed with protamines. These proteins need to be removed in the zygote and replaced by maternally provided histones before the paternal genome acquires competence for replication, a prerequisite for syngamy. All these events must be highly coordinated to allow the first zygotic nucleus to form with the two sets of parental chromosomes and enter the first mitotic cycle. Our laboratory has identified yemanuclein-alpha, also called yemanuclein (yem) in a molecular screen for genes specifically expressed in the female germ line and its first mutant allele yem1, in a female sterile screen. The role played by yem not only in the meiotic process through which a haploid maternal pronucleus is formed but also in the zygotic process that makes a paternal pronucleus competent for syngamy, is underscored by the obtention of exceptional parthenogenetic progeny from yem1 mothers.My thesis work is precisely dedicated to the analysis of both aspects of Yemanuclein function: in the oocyte and the zygote. Using genetic, biochemical and cell biology methods we were able to uncover essential functions of Yemanuclein in early meiotic prophase in the Drosophila oocyte. Using yem1 allele (V478E), we could show its requirement for meiotic recombination especially for the frequency and timing of the double strand breaks formation. Yemanuclein association with two protein complexes, the Synaptonemal Complex (SC) and the Cohesin complex known to be required for proper chromosome segregation, supports these findings. Beyond its meiotic function, Yemanuclein is also required in the zygote for assembly of paternal pronucleus chromatin. This is achieved through a third complex that acts as histone H3.3 chaperone. In the present manuscript we identify Yemanuclein as a partner of HIRA in its role in H3.3 nucleosome assembly and deposition on the paternal pronucleus. Interestingly Yemanuclein is the first member of the HPC2/UBN1 protein family ever characterized. The role of Yem/ HPC2/ UBN1 in replication independent chromatin remodeling remained elusive until very recently. Our work is original in that it is the first to report on a role of one member of this family in oocyte meiosis and paternal chromatin assembly in the zygote.
2 citations
Cites background from "Epigenetic codes in cognition and b..."
...Figure 17: Schematic representation of post-translational histone modifications Prevalent post-translational histone modifications of the N- and C-termini of the core histones and their residue-specific epigenetic modifications include methylation (green M boxes) of lysine and arginine, acetylation (yellow A pentagon) of lysine, phosphorylation (red P sphere) of threonine or serine and ubiquitination (blue U triangle) of lysine residues (Graff and Mansuy, 2008)....
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...…histones and their residue-specific epigenetic modifications include methylation (green M boxes) of lysine and arginine, acetylation (yellow A pentagon) of lysine, phosphorylation (red P sphere) of threonine or serine and ubiquitination (blue U triangle) of lysine residues (Graff and Mansuy, 2008)....
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Journal Article•
TL;DR: In this article, a comparison of the eficacia atencional in escolares argentinos with those who asisten to escuelas publica and privatea is presented.
Abstract: Introduccion.
La Eficacia Atencional (EA) es definida como la exactitud con la cual un nina/o discrimina estimulos iguales a un modelo, dentro de un conjunto de estimulos semejantes, en un tiempo determinado. Diversos factores pueden asociarse a una mayor o menor EA,
entre ellos el contexto socieconomico. Los objetivos de este estudio fueron: 1) describir la eficacia atencional en escolares argentinos segun el tipo de escuela a la cual asisten (privada-publica), segun la edad y el genero de los escolares y segun el nivel educativo y ocupacional de las madres de los escolares; 2) comparar la eficacia atencional segun el tipo de escuela (privada-publica), segun la edad y el genero de los escolares y segun el nivel educativo y ocupacional de las madres de los escolares.
Metodo.
Se utilizo un estudio comparativo de tipo trasversal. Se conformaron dos grupos de
escolares de 10 a 13 anos de edad: 74 pertenecientes a escuelas publicas (M = 11.26; DS= 0.93; 53% varones y 47% ninas) y 67 escolares (M = 11.49; DS= 1.05; 54% varones y 46% ninas) pertenecientes a una escuela privada. El tipo de escuela es caracterizada segun la Direccion General de Escuela. Las escuelas privadas estan ubicadas en zonas urbanas. Las escuelas publicas estan localizadas en areas perifericas en contextos de vulnerabilidad social. La vulnerabilidad social es una condicion social de riesgo que dificulta en el presente o futuro la satisfaccion del bienestar en tanto subsistencia y calidad de vida. En este tipo de contextos existen bajos niveles educativos en las familias, condiciones laborales precarias, familias disfuncionales y deficitarios servicios de salud para las madres y sus hijos. Todas estas situaciones conllevan a una condicion social de desigualdad y de disminucion de oportunidades para
el desarrollo infantil. En Guaymallen, Mendoza, hay 10 escuelas publicas en zonas perifericas y 25 escuelas privadas. Los participantes provienen de dos escuelas, una publica y otra privada de dicha localidad.
Resultados.
Los resultados indicaron una menor eficacia atencional en escolares que concurren a escuelas publicas en comparacion con aquellos que asisten a una escuela privada. No se
registraron diferencias estadisticamente signitivativas en eficacia atencional en relacion al genero o a la edad de los escolares participantes. Los escolares cuyas ma
dres obtuvieron un nivel universitario obtuvieron un desempeno atencional significativamente superior en comparacion con los escolares cuyas madres presentaron un nivel de escolaridad primaria Ademas, los escolares cuyas madres
eran laboralmente activas presentaron un desempeno atencional significativamente mayor en comparacion con los escolares cuyas madres estaban desocupadas. Sin embargo, no se observaron diferencias significativas en el desempeno atencional de los ninos en relacion a la clasificacion ocupacional de sus madres.
Conclusion.
Este trabajo coincide con investigaciones que muestran la influencia del contexto
socioeconomico sobre el desempeno atencional de los ninos, aportando evidencia sobre la necesidad de adecuar las practicas educativas e intervenciones cognitivas a fin de potenciar los logros academicos de los ninos
2 citations
Cites background from "Epigenetic codes in cognition and b..."
...Cognitive performance may be modified by epigenetic mechanisms, suggesting that experience has a strong influence on genetic expression and the resulting cognitive performance scores (Gräff & Mansuy, 2008; Hackman & Farah, 2009)....
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Dissertation•
21 Sep 2015
TL;DR: The results of this work provide support to the neuroplasticity hypothesis of depression, from both developmental and activational perspectives and suggest putative etiopathogenic pathways leading from an altered early neurodevelopment to an increased risk for depression-related phenotypes.
Abstract: In the behavioral sciences, the concept of phenotypic plasticity can be roughly categorized into two classes: developmental and activational plasticity. Developmental plasticity denotes the capacity of an individual carrying a specific genetic background to adopt different developmental trajectories under distinct settings. Complementarily, activational plasticity refers to the differential activation of adaptation mechanisms: an individual with high activational plasticity would be able to detect a wide range of environments, and to respond to it using a psychobiological phenotype from a relatively large catalogue. In this context, it is feasible postulating that several etiopathogenic mechanisms of depression-related phenotypes can be clarified by expanding on processes of biobehavioral plasticity in response to the experience. This expansion can be elaborated on the basis of both neurodevelopmental phenomena (developmental plasticity) and novel biological mechanisms detectable through neuroimaging and epigenetics approaches (activational plasticity). The present work expands on two specific hypotheses. First, depression-related psychopathological phenotypes are induced by factors altering the early neurodevelopment, and these long-lasting changes can be assessed in adulthood (depression and developmental plasticity). Secondly, the clinical manifestation of depression-related psychopathological phenotypes can be understood as activational plasticity deficits; these deficits can be assessed as neurobiological disease traits using novel epigenetic and neuroimaging techniques (depression and activational plasticity). The results of this work provide support to the neuroplasticity hypothesis of depression, from both developmental and activational perspectives. Developmentally, they suggest putative etiopathogenic pathways leading from an altered early neurodevelopment to an increased risk for depression-related phenotypes. By exploring and combining genetic, environmental and psychopathologic concepts, the feasibility of these results has been explained by combining the popular genetic pleiotropy hypothesis in psychiatry with a notion of disease-specificity liability driven by the environment. With regards to activational plasticity, this work has proposed novel genetic and epigenetic signatures potentially underlying the clinical manifestation of neuropsychiatric and neurocognitive features of depression (i.e., the genetics of DNMT3B and the epigenetics of DEPDC7); additionally, it has proposed new putative neurobiological mechanisms to explain depressive traits (i.e., a combination of differential and variable methylation, a genetically-mediated hippocampal communication deficit, and a new amygdalar synchrony failure driven by the genes).
2 citations
Dissertation•
01 Jan 2016
2 citations
Cites background from "Epigenetic codes in cognition and b..."
...…development of a number of diseases including cancer (Christoph et al., 2008), cardiovascular disease (Stenvinkel et al., 2007), hypertension (Smolarek et al., 2010), autoimmune diseases and neurological diseases such as Parkinson’s and Alzheimer’s diseases (Gräff & Mansuy, 2008; Liu et al., 2011)....
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References
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TL;DR: The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.
Abstract: Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.
11,123 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...These forms f plasticity reflect respectively, an increase and a decrease in he efficiency of synaptic transmission, and have been extenively studied in the hippocampus, a brain area required for earning and memory (for a review see [30])....
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TL;DR: The surface of nucleosomes is studded with a multiplicity of modifications that can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA.
10,046 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...Chronic xposure to an aggressor results in pronounced social avoidnce, prolonged downregulation of two splice variants of Bdnf, dnfIII and BdnfIV in the hippocampus and increased promoter imethylation of H3K27 [102], a mark of transcriptional represion [20]....
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TL;DR: It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
Abstract: Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. The combinatorial nature of histone amino-terminal modifications thus reveals a “histone code” that considerably extends the information potential of the genetic code. We propose that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
9,309 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...These nzymes operate both independently and in synergy to establish “histone code”, a highly dynamic and flexible chromatin markng that, in combination with chromatin-associated proteins, etermines the pattern of gene expression in response to given xternal stimuli [24,25]....
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TL;DR: The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development.
Abstract: The character of a cell is defined by its constituent proteins, which are the result of specific patterns of gene expression. Crucial determinants of gene expression patterns are DNA-binding transcription factors that choose genes for transcriptional activation or repression by recognizing the sequence of DNA bases in their promoter regions. Interaction of these factors with their cognate sequences triggers a chain of events, often involving changes in the structure of chromatin, that leads to the assembly of an active transcription complex (e.g., Cosma et al. 1999). But the types of transcription factors present in a cell are not alone sufficient to define its spectrum of gene activity, as the transcriptional potential of a genome can become restricted in a stable manner during development. The constraints imposed by developmental history probably account for the very low efficiency of cloning animals from the nuclei of differentiated cells (Rideout et al. 2001; Wakayama and Yanagimachi 2001). A “transcription factors only” model would predict that the gene expression pattern of a differentiated nucleus would be completely reversible upon exposure to a new spectrum of factors. Although many aspects of expression can be reprogrammed in this way (Gurdon 1999), some marks of differentiation are evidently so stable that immersion in an alien cytoplasm cannot erase the memory. The genomic sequence of a differentiated cell is thought to be identical in most cases to that of the zygote from which it is descended (mammalian B and T cells being an obvious exception). This means that the marks of developmental history are unlikely to be caused by widespread somatic mutation. Processes less irrevocable than mutation fall under the umbrella term “epigenetic” mechanisms. A current definition of epigenetics is: “The study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence” (Russo et al. 1996). There are two epigenetic systems that affect animal development and fulfill the criterion of heritability: DNA methylation and the Polycomb-trithorax group (Pc-G/trx) protein complexes. (Histone modification has some attributes of an epigenetic process, but the issue of heritability has yet to be resolved.) This review concerns DNA methylation, focusing on the generation, inheritance, and biological significance of genomic methylation patterns in the development of mammals. Data will be discussed favoring the notion that DNA methylation may only affect genes that are already silenced by other mechanisms in the embryo. Embryonic transcription, on the other hand, may cause the exclusion of the DNA methylation machinery. The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development. Indeed, the possibility will be discussed that DNA methylation and Pc-G/trx may represent alternative systems of epigenetic memory that have been interchanged over evolutionary time. Animal DNA methylation has been the subject of several recent reviews (Bird and Wolffe 1999; Bestor 2000; Hsieh 2000; Costello and Plass 2001; Jones and Takai 2001). For recent reviews of plant and fungal DNA methylation, see Finnegan et al. (2000), Martienssen and Colot (2001), and Matzke et al. (2001).
6,691 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...ecause of the covalent nature of the binding of methyl groups o the C5 carbon in cytosine, DNA methylation is thought to be he most stable epigenetic mark [9]....
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...DNA methylation is commonly associated with ranscriptional silencing because it can directly inhibit the bindng of transcription factors or regulators, or indirectly recruit ethyl-CpG binding proteins (MBPs), which have repressive hromatin-remodeling functions [9,10]....
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...Most cases of RS are caused by mutaions in the gene coding for methyl-CpG binding protein 2 MeCP2) [62], a member of the MBP family involved in ong-term gene silencing (for a review see [9])....
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TL;DR: Advances in the understanding of the mechanism and role of DNA methylation in biological processes are reviewed, showing that epigenetic mechanisms seem to allow an organism to respond to the environment through changes in gene expression.
Abstract: Cells of a multicellular organism are genetically homogeneous but structurally and functionally heterogeneous owing to the differential expression of genes. Many of these differences in gene expression arise during development and are subsequently retained through mitosis. Stable alterations of this kind are said to be 'epigenetic', because they are heritable in the short term but do not involve mutations of the DNA itself. Research over the past few years has focused on two molecular mechanisms that mediate epigenetic phenomena: DNA methylation and histone modifications. Here, we review advances in the understanding of the mechanism and role of DNA methylation in biological processes. Epigenetic effects by means of DNA methylation have an important role in development but can also arise stochastically as animals age. Identification of proteins that mediate these effects has provided insight into this complex process and diseases that occur when it is perturbed. External influences on epigenetic processes are seen in the effects of diet on long-term diseases such as cancer. Thus, epigenetic mechanisms seem to allow an organism to respond to the environment through changes in gene expression. The extent to which environmental effects can provoke epigenetic responses represents an exciting area of future research.
5,760 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...ot be explained by changes in the DNA sequence itself [3] reviewed in [4,5])....
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