scholarly journals Regulation of mRNA splicing by MeCP2 via epigenetic modifications in the brain

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Tian-Lin Cheng ◽  
Jingqi Chen ◽  
Huida Wan ◽  
Bin Tang ◽  
Weidong Tian ◽  
...  
Keyword(s):  
Epigenetic Modifications ◽  
Mrna Splicing ◽  
Modifications In The Brain ◽  
The Brain

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 Methylmercury Epigenetics

Toxics ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 56 ◽  
Author(s):  
Megan Culbreth ◽  
Michael Aschner
Keyword(s):  
Dna Methylation ◽  
Mirna Expression ◽  
Epigenetic Modifications ◽  
Nervous System Development ◽  
Gene Promoters ◽  
Toxic Response ◽  
The Impact ◽  
The Brain

Methylmercury (MeHg) has conventionally been investigated for effects on nervous system development. As such, epigenetic modifications have become an attractive mechanistic target, and research on MeHg and epigenetics has rapidly expanded in the past decade. Although, these inquiries are a recent advance in the field, much has been learned in regards to MeHg-induced epigenetic modifications, particularly in the brain. In vitro and in vivo controlled exposure studies illustrate that MeHg effects microRNA (miRNA) expression, histone modifications, and DNA methylation both globally and at individual genes. Moreover, some effects are transgenerationally inherited, as organisms not directly exposed to MeHg exhibited biological and behavioral alterations. miRNA expression generally appears to be downregulated consequent to exposure. Further, global histone acetylation also seems to be reduced, persist at distinct gene promoters, and is contemporaneous with enhanced histone methylation. Moreover, global DNA methylation appears to decrease in brain-derived tissues, but not in the liver; however, selected individual genes in the brain are hypermethylated. Human epidemiological studies have also identified hypo- or hypermethylated individual genes, which correlated with MeHg exposure in distinct populations. Intriguingly, several observed epigenetic modifications can be correlated with known mechanisms of MeHg toxicity. Despite this knowledge, however, the functional consequences of these modifications are not entirely evident. Additional research will be necessary to fully comprehend MeHg-induced epigenetic modifications and the impact on the toxic response.

scholarly journals Epigenetic Regulation of Gene Expression in Physiological and Pathological Brain Processes

2011 ◽  
Vol 91 (2) ◽  
pp. 603-649 ◽  
Author(s):  
Johannes Gräff ◽  
Dohoon Kim ◽  
Matthew M. Dobbin ◽  
Li-Huei Tsai
Keyword(s):  
Regulation Of Gene Expression ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanisms ◽  
Brain Functions ◽  
Epigenetic Machinery ◽  
Complex Functions ◽  
Cell Type Specific ◽  
Neuronal Functions ◽  
The Brain ◽  
Unique Potential

Over the past decade, it has become increasingly obvious that epigenetic mechanisms are an integral part of a multitude of brain functions that range from the development of the nervous system over basic neuronal functions to higher order cognitive processes. At the same time, a substantial body of evidence has surfaced indicating that several neurodevelopmental, neurodegenerative, and neuropsychiatric disorders are in part caused by aberrant epigenetic modifications. Because of their inherent plasticity, such pathological epigenetic modifications are readily amenable to pharmacological interventions and have thus raised justified hopes that the epigenetic machinery provides a powerful new platform for therapeutic approaches against these diseases. In this review, we give a detailed overview of the implication of epigenetic mechanisms in both physiological and pathological brain processes and summarize the state-of-the-art of “epigenetic medicine” where applicable. Despite, or because of, these new and exciting findings, it is becoming apparent that the epigenetic machinery in the brain is highly complex and intertwined, which underscores the need for more refined studies to disentangle brain-region and cell-type specific epigenetic codes in a given environmental condition. Clearly, the brain contains an epigenetic “hotspot” with a unique potential to not only better understand its most complex functions, but also to treat its most vicious diseases.

Histone modifications in the brain

2007 ◽  
Vol 51 (2-4) ◽  
pp. 85-91 ◽  
Author(s):  
Hideo Taniura ◽  
Judy C.G. Sng ◽  
Yukio Yoneda
Keyword(s):  
Histone Modifications ◽  
Modifications In The Brain ◽  
The Brain

scholarly journals Regulation of neuronal mRNA splicing and Tau isoform ratio by ATXN3 through deubiquitylation of splicing factors

2019 ◽  
Author(s):  
Andreia Neves-Carvalho ◽  
Sara Duarte-Silva ◽  
Joana Silva ◽  
Bruno Almeida ◽  
Sasja Heetveld ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Rna Metabolism ◽  
Mrna Splicing ◽  
Splicing Factors ◽  
Loss Of Function ◽  
Relevant Role ◽  
The Brain ◽  
Precise Role ◽  
Exon 10

ABSTRACTThe ubiquitylation/deubiquitylation balance in cells is maintained by Deubiquitylating enzymes, including ATXN3. The precise role of this protein, mutated in SCA3, remains elusive, as few substrates for its deubiquitylating activity were identified. Therefore, we characterized the ubiquitome of neuronal cells lacking ATXN3, and found altered polyubiquitylation in a large proportion of proteins involved in RNA metabolism, including splicing factors. Using transcriptomic analysis and reporter minigenes we confirmed that splicing was globally altered in these cells. Among the targets with altered splicing was SRSF7 (9G8), a key regulator of MAPT (Tau) exon 10 splicing. Loss-of-function of ATXN3 led to a deregulation of MAPT exon 10 splicing resulting in a decreased 4R/3R-Tau ratio. Similar alterations were found in the brain of a SCA3 mouse and humans, pointing to a relevant role of this mechanism in SCA3, and establishing a previously unsuspected link between two key proteins involved in different neurodegenerative disorders.

scholarly journals RES complex is associated with intron definition and required for zebrafish early embryogenesis

2017 ◽  
Author(s):  
Juan P. Fernandez ◽  
Miguel A. Moreno-Mateos ◽  
Andre Gohr ◽  
Shun Hang Chan ◽  
Manuel Irimia ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Splicing ◽  
Vertebrate Development ◽  
Loss Of Function ◽  
Recognition Elements ◽  
Splicing Patterns ◽  
The Brain ◽  
Intron Definition

AbstractPre-mRNA splicing is a critical step of gene expression in eukaryotes. Transcriptome-wide splicing patterns are complex and primarily regulated by a diverse set of recognition elements and associated RNA-binding proteins. The retention and splicing (RES) complex is formed by three different proteins (Bud13p, Pml1p and Snu17p) and is involved in splicing in yeast. However, the importance of the RES complex for vertebrate splicing, the intronic features associated with its activity, and its role in development are unknown. In this study, we have generated loss-of-function mutants for the three components of the RES complex in zebrafish and showed that they are required during early development. The mutants showed a marked neural phenotype with increased cell death in the brain and a decrease in differentiated neurons. Transcriptomic analysis of bud13, snip1 (pml1) and rbmx2 (snu17) mutants revealed a global defect in intron splicing, with strong mis-splicing of a subset of introns. We found these RES-dependent introns were short, rich in GC and flanked by GC depleted exons, all of which are features associated with intron definition. Using these features we developed a predictive model that classifies RES dependent introns. Altogether, our study uncovers the essential role of the RES complex during vertebrate development and provides new insights into its function during splicing.

Bilirubin and Epigenetic Modifications in Metabolic and Immunometabolic Disorders

2021 ◽  
Vol 21 ◽  
Author(s):  
Mostafa Moradi Sarabi ◽  
Esmaeel Babaeenezhad ◽  
Maral Amini ◽  
Mozhgan Kaviani ◽  
Fakhraddin Naghibalhossaini
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Waste Product ◽  
Epigenetic Modifications ◽  
Mechanisms Of Toxicity ◽  
High Concentrations ◽  
The Brain

: Bilirubin is the main waste product of heme catabolism. At high concentrations, bilirubin may cause toxicity, especially in the brain, kidney, and erythrocytes. Membrane and mitochondrial dysfunction, oxidative stress, apoptosis, necrosis, endoplasmic reticulum stress, excitotoxicity, inflammation, and epigenetic modifications are the main mechanisms of toxicity triggered by bilirubin in susceptible organs. Many studies have shown that there is an interaction between bilirubin and epigenetic modifications in metabolic and immune diseases. In this review, we first outline the toxicity mediated by bilirubin and then summarize the current knowledge linking bilirubin and epigenetic modifications in metabolic and immunometabolic disorders.

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