ATRX Partners with Cohesin and MeCP2 and Contributes to Developmental Silencing of Imprinted Genes in the Brain

Kernohan, Kristin D.; Jiang, Yan; Tremblay, Deanna C.; Bonvissuto, Anne C.; Eubanks, James H.; Mann, Mellissa R.W.; Bérubé, Nathalie G.

doi:10.1016/j.devcel.2009.12.017

Cited by 159 publications

(139 citation statements)

References 60 publications

(78 reference statements)

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“…Gabory et al (2009) also demonstrated that such regulation via H19 apparently did not operate in the placenta, which implies a notable degree of tissue and stage specificity of imprinted-gene network dynamics. Most recently, loss of expression of the ATRX gene in mice has been shown to cause altered postnatal expression of a suite of imprinted genes including Igf2, H19, Dlk1, Zac1, and Peg1, as well as the Rett-syndrome gene MeCP2, suggesting a role for ATRX in transregulation of the imprinted-gene network (Kernohan et al 2010) and corroborating effects of MeCP2 expression in the regulation of imprinted genes (Miyano et al 2008).…”

Section: Introductionmentioning

confidence: 99%

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

Crespi

2011

Brain, Behavior and Epigenetics

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I describe and evaluate the hypothesis that effects from parent-offspring conflict and genomic imprinting on human neurodevelopment and behavior are central to evolved systems of mother-child attachment. The psychological constructs of Bowlby's attachment theory provide phenomenological descriptions of how attachment orchestrates affective-cognitive development, and patterns of imprinted gene expression and co-expression provide evidence of epigenetic and evolutionary underpinnings to human growth and neurodevelopment. Social-environmental perturbations to the development of normally-secure attachment, and alterations to evolved systems of parent-offspring conflict and imprinted-gene effects, are expected to lead to specific forms of maladaptation, manifest in psychiatric conditions affecting social-brain development. In particular, under-development of the social brain in autism may be mediated in part by mechanisms that lead to physically enhanced yet psychologically under-developed attachment to the mother, and affective-psychotic conditions, such as schizophrenia and depression, may be mediated in part by forms of insecure attachment and by increased relative effects of the maternal brain, both directly from mothers and via imprinted-gene effects in offspring. These hypotheses are concordant with findings from epidemiology, attachment theory, psychiatry, and genetic and epigenetic analyses of risk factors for autism and affective-psychotic conditions, they make novel predictions for explaining the causes of psychosis in Prader-Willi syndrome and idiopathic schizophrenia, and they suggest avenues for therapeutic interventions based on normalizing alterations to epigenetic networks and targeting public-health interventions towards reduction of perturbations to the development of secure attachment in early childhood and individuation during adolescence.

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Section: Introductionmentioning

confidence: 99%

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

Crespi

2011

Brain, Behavior and Epigenetics

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“…Atrx has been shown to be critical for mouse extraembryonic trophoblast formation and subsequent embryo survival 9.5 d postcoitus and is also involved in developmental silencing of imprinted genes [Kernohan et al 2010] and may prove to be a non-invasive marker of an oocyte's developmental competence. Markers in the cumulus cells that surround the oocyte are of particular interest allowing for a non-invasive method of detecting oocyte quality without destroying the oocyte in the process.…”

Section: Discussionmentioning

confidence: 99%

Developmental competence in oocytes and cumulus cells: candidate genes and networks

O'Shea

Mehta

Lonergan

et al. 2012

Systems Biology in Reproductive Medicine

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Common aspects of infertility can be seen across several species. In humans, dairy cows, and mares there is only a 25-35% chance of producing a live offspring after a single insemination, whether natural or artificial. Oocyte quality and subsequent embryo development can be affected by factors such as nutrition, hormonal regulation, and environmental influence. The objective of this study was to identify genes expressed in oocytes and/ or cumulus cells, across a diverse range of species, which may be linked to the ability an oocyte has to develop following fertilization. Performing a meta-analysis on previously published microarray data on various models of oocyte and embryo quality allowed for the identification of 56 candidate genes associated with oocyte quality across several species, 4 of which were identified in the cumulus cells that surround the oocyte. Twenty-one potential biomarkers were associated with increased competence and 35 potential biomarkers were associated with decreased competence. The upregulation of Metap2, and the decrease of multiple genes linked to mRNA and protein synthesis in models of competence, highlights the importance of de novo protein synthesis and its regulation for successful oocyte maturation and subsequent development. The negative regulation of Wnt signaling has emerged in human, monkey, bovine, and mouse models of oocyte competence. Atrx expression was linked to decreased competence in both oocytes and cumulus cells. Biological networks and transcription factor regulation associated with increased and decreased competence were also identified. These genes could potentially act as biomarkers of oocyte quality or as pharmacological targets for manipulation in order to improve oocyte developmental potential.

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“…Furthermore, Mecp2 directly regulates a large cluster of mi-RNAs within the Dlk1-Gtl2 imprinting domain. Kernohan et al (2010) pointed out that the methylation region close to the Gtl2 promoter is associated with X-linked a thalassemia/mental retardation syndrome (168 patients reported in the European Community), suggesting a role for Mecp2 in the transcriptional control of this region.…”

Section: Rare Diseases May Share Common Pathophysiological Mechanismsmentioning

confidence: 99%

From Molecules to Behavior: Lessons from the Study of Rare Genetic Disorders

Roubertoux

Vries

2011

Behav Genet

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Rare diseases are defined as conditions with a prevalence of less than 1/2,000. To date between 6,000 and 7,000 rare diseases have been identified and many of those have manifestations that include intellectual disability, developmental disorders or other behavioural phenotypes. In this special issue we bring together a range of papers where rare diseases were used as models to delineate specific aspects of learning and memory, or behaviour. In this introductory paper we summarize some of the lessons we can learn from rare diseases. Firstly, we learn that, collectively, rare diseases are not at all rare. As many as 1 in 20 individuals may be affected by a rare disease at some point in their life. Secondly, we learn that rare diseases may share common pathophysiological mechanisms. A discovery in one can therefore have direct relevance to many others. A third lesson is that the study of rare diseases can lead to an understanding of common disorders, as exemplified by the relationship between Trisomy 21 (Down syndrome) and Alzheimer's disease. A fourth lesson from rare diseases is that the 'one gene-one functional consequence' assumption is not correct. Finally, rare diseases have shed new light on the strengths and weaknesses of animal models in the study of behavioural phenotypes.

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ATRX Partners with Cohesin and MeCP2 and Contributes to Developmental Silencing of Imprinted Genes in the Brain

Cited by 159 publications

References 60 publications

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

Developmental competence in oocytes and cumulus cells: candidate genes and networks

From Molecules to Behavior: Lessons from the Study of Rare Genetic Disorders

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