scholarly journals Epigenetic mechanisms in sexual differentiation of the brain and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Wide Distribution ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
The Brain

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.

scholarly journals Sex Differences in the Epigenome: A Cause or Consequence of Sexual Differentiation of the Brain?

Genes ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 432 ◽  
Author(s):  
Bruno Gegenhuber ◽  
Jessica Tollkuhn
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Hormone Receptors ◽  
Neurological Diseases ◽  
Activity Patterns ◽  
Regulatory Elements ◽  
The Body ◽  
Epigenetic Mechanism ◽  
The Brain

Females and males display differences in neural activity patterns, behavioral responses, and incidence of psychiatric and neurological diseases. Sex differences in the brain appear throughout the animal kingdom and are largely a consequence of the physiological requirements necessary for the distinct roles of the two sexes in reproduction. As with the rest of the body, gonadal steroid hormones act to specify and regulate many of these differences. It is thought that transient hormonal signaling during brain development gives rise to persistent sex differences in gene expression via an epigenetic mechanism, leading to divergent neurodevelopmental trajectories that may underlie sex differences in disease susceptibility. However, few genes with a persistent sex difference in expression have been identified, and only a handful of studies have employed genome-wide approaches to assess sex differences in epigenomic modifications. To date, there are no confirmed examples of gene regulatory elements that direct sex differences in gene expression in the brain. Here, we review foundational studies in this field, describe transcriptional mechanisms that could act downstream of hormone receptors in the brain, and suggest future approaches for identification and validation of sex-typical gene programs. We propose that sexual differentiation of the brain involves self-perpetuating transcriptional states that canalize sex-specific development.

scholarly journals DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral modelAiptasia

2017 ◽  
Author(s):  
Yong Li ◽  
Yi Jin Liew ◽  
Guoxin Cui ◽  
Maha J Cziesielski ◽  
Noura Zahran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Model System ◽  
Epigenetic Mechanism ◽  
Symbiotic Relationship ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
Spurious Transcription ◽  
Coral Reef Ecosystems

The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model systemAiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

scholarly journals Recent progress towards understanding the role of DNA methylation in human placental development

Reproduction ◽  
2016 ◽  
Vol 152 (1) ◽  
pp. R23-R30 ◽  
Author(s):  
Tina Bianco-Miotto ◽  
Benjamin T Mayne ◽  
Sam Buckberry ◽  
James Breen ◽  
Carlos M Rodriguez Lopez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Pregnancy Complications ◽  
Large Scale ◽  
Developmental Stages ◽  
Epigenetic Modifications ◽  
Placental Development ◽  
Functional Changes ◽  
Genome Wide

Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses.

scholarly journals Epigenetics of obesity

2020 ◽  
Vol 19 (6) ◽  
pp. 2632
Author(s):  
O. M. Drapkina ◽  
O. T. Kim
Keyword(s):  
Gene Expression ◽  
Deoxyribonucleic Acid ◽  
Fat Distribution ◽  
Epigenetic Modifications ◽  
Lifestyle Changes ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Critical Periods ◽  
Affect Gene Expression

The pathophysiology of obesity is complex and includes changes in eating behavior, genetic, epigenetic, environmental factors, and much more. To date, ~40 genetic polymorphisms are associated with obesity and fat distribution. However, since these options do not fully explain the inheritance of obesity, other options, such as epigenetic changes, need to be considered. Epigenetic modifications affect gene expression without changing the deoxyribonucleic acid sequence. In addition, environmental exposure during critical periods of development can affect the epigenetic tags and lead to obesity. A deeper understanding of the epigenetic mechanisms underlying obesity can aid in prevention based on lifestyle changes. This review focuses on the role of epigenetic modifications in the development of obesity and related conditions.

scholarly journals High-throughput sequencing offers new insights into 5-hydroxymethylcytosine

2016 ◽  
Vol 7 (3) ◽  
pp. 169-178 ◽  
Author(s):  
Alina P.S. Pang ◽  
Christopher Sugai ◽  
Alika K. Maunakea
Keyword(s):  
High Throughput Sequencing ◽  
Wide Distribution ◽  
Clinical Applications ◽  
Specific Nature ◽  
Functional Roles ◽  
Disease States ◽  
Tet Proteins ◽  
Genome Wide ◽  
The Brain

AbstractChemical modifications of DNA comprise epigenetic mechanisms that contribute to the maintenance of cellular activities and memory. Although the function of 5-methylcytosine (5-mC) has been extensively studied, little is known about the function(s) of relatively rarer and underappreciated cytosine modifications including 5-hydroxymethylcytosine (5-hmC). The discovery that ten-eleven translocation (Tet) proteins mediate conversion of 5-mC to 5-hmC, and other oxidation derivatives, sparked renewed interest to understand the biological role of 5-hmC. Studies examining total 5-hmC levels revealed the highly dynamic yet tissue-specific nature of this modification, implicating a role in epigenetic regulation and development. Intriguingly, 5-hmC levels are highest during early development and in the brain where abnormal patterns of 5-hmC have been observed in disease conditions. Thus, 5-hmC adds to the growing list of epigenetic modifications with potential utility in clinical applications and warrants further investigation. This review discusses the emerging functional roles of 5-hmC in normal and disease states, focusing primarily on insights provided by recent studies exploring the genome-wide distribution of this modification in mammals.

The role of epigenetics in social psychiatry

2016 ◽  
Vol 63 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Jacob Peedicayil
Keyword(s):  
Gene Expression ◽  
Psychiatric Disorders ◽  
Psychosocial Factors ◽  
Dna Sequence ◽  
Social Psychiatry ◽  
Epigenetic Mechanisms ◽  
Peripheral Tissues ◽  
The Brain ◽  
Brain Tissues

Background: Epigenetics refers to the study of heritable changes in gene expression not involving changes in DNA sequence and is presently an active area of research in biology and medicine. There is increasing evidence that epigenetics is involved in the pathogenesis of psychiatric disorders. Aims and Methods: Several studies conducted to date have suggested that psychosocial factors act by modifying epigenetic mechanisms of gene expression in the brain in the pathogenesis of psychiatric disorders. Such studies have been conducted both on brain tissues and also using peripheral tissues as substitutes for brain tissues. This article reviews such studies. Results and Conclusion: Epigenetic mechanisms of gene expression in the brain appear to link one individual with another in the context of social psychiatry. Epigenetics appears to be of major importance to the field of social psychiatry.

Alcohol Use Disorder

2018 ◽  
Author(s):  
Igor Ponomarev
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Critical Discussion ◽  
Epigenetic Mechanisms ◽  
Future Directions ◽  
Clinically Significant ◽  
Early Life Exposures ◽  
The Brain ◽  
Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

scholarly journals Leveraging epigenetics to enhance the efficacy of immunotherapy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jonathan D. Licht ◽  
Richard L. Bennett
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Antigen Presentation ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Epigenetic Modifications ◽  
Main Body ◽  
Epigenetic Mechanisms

Abstract Background Epigenetic mechanisms regulate chromatin accessibility patterns that govern interaction of transcription machinery with genes and their cis-regulatory elements. Mutations that affect epigenetic mechanisms are common in cancer. Because epigenetic modifications are reversible many anticancer strategies targeting these mechanisms are currently under development and in clinical trials. Main body Here we review evidence suggesting that epigenetic therapeutics can deactivate immunosuppressive gene expression or reprogram tumor cells to activate antigen presentation mechanisms. In addition, the dysregulation of epigenetic mechanisms commonly observed in cancer may alter the immunogenicity of tumor cells and effectiveness of immunotherapies. Conclusions Therapeutics targeting epigenetic mechanisms may be helpful to counter immune evasion and improve the effectiveness of immunotherapies.

scholarly journals Bile Acids in Dementia: Brain Amyloid, White Matter Lesions, and Atrophy

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 767-768
Author(s):  
Vijay Varma ◽  
Youjin Wang ◽  
Yang An ◽  
Sudhir Varma ◽  
Murat Bilgel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acids ◽  
White Matter Lesions ◽  
Pharmacological Modulation ◽  
Dementia Risk ◽  
The Brain ◽  
Step Study ◽  
Brain Amyloid Deposition ◽  
Gene Expression Levels

Abstract While Alzheimer’s disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association is unclear. Using a novel, 3-step study design we examined the role of cholesterol catabolism in dementia by testing whether 1) the synthesis of the primary cholesterol breakdown products (bile acids (BA)) were associated with neuroimaging markers of dementia; 2) pharmacological modulation of BAs alters dementia risk; and 3) brain BA concentrations and gene expression were associated with AD. We found that higher serum concentrations of BAs are associated with lower brain amyloid deposition, slower WML accumulation, and slower brain atrophy in males. Opposite effects were observed in females. Modulation of BA levels alters risk of incident VaD in males. Altered brain BA signaling at the metabolite and gene expression levels occurs in AD. Dysregulation of peripheral cholesterol catabolism and BA synthesis may impact dementia pathogenesis through signaling pathways in the brain.

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