scholarly journals Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Sebastian Ocklenburg ◽  
Judith Schmitz ◽  
Zahra Moinfar ◽  
Dirk Moser ◽  
Rena Klose ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Epigenetic Regulation ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Cpg Islands ◽  
Fundamental Principle ◽  
Human Fetuses ◽  
Hemispheric Asymmetries ◽  
Starting Point

Lateralization is a fundamental principle of nervous system organization but its molecular determinants are mostly unknown. In humans, asymmetric gene expression in the fetal cortex has been suggested as the molecular basis of handedness. However, human fetuses already show considerable asymmetries in arm movements before the motor cortex is functionally linked to the spinal cord, making it more likely that spinal gene expression asymmetries form the molecular basis of handedness. We analyzed genome-wide mRNA expression and DNA methylation in cervical and anterior thoracal spinal cord segments of five human fetuses and show development-dependent gene expression asymmetries. These gene expression asymmetries were epigenetically regulated by miRNA expression asymmetries in the TGF-β signaling pathway and lateralized methylation of CpG islands. Our findings suggest that molecular mechanisms for epigenetic regulation within the spinal cord constitute the starting point for handedness, implying a fundamental shift in our understanding of the ontogenesis of hemispheric asymmetries in humans.

Molecular mechanisms underlying the regulation of proenkephalin gene expression in cultured spinal cord cells

Neuropeptides ◽  
1996 ◽  
Vol 30 (5) ◽  
pp. 506-513 ◽  
Author(s):  
T.-S Ha ◽  
Y.-H Kim ◽  
D.-K Song ◽  
M.-B Wie ◽  
H.W Suh
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Molecular Mechanisms

scholarly journals Size Matters: An Evaluation of the Molecular Basis of Ontogenetic Modifications in the Composition of Bothrops jararacussu Snake Venom

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 791
Author(s):  
Luciana A. Freitas-de-Sousa ◽  
Pedro G. Nachtigall ◽  
José A. Portes-Junior ◽  
Matthew L. Holding ◽  
Gunnar S. Nystrom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Snake Venom ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Venom Gland ◽  
Ontogenetic Changes ◽  
Bothrops Jararacussu ◽  
Phospholipases A2 ◽  
Venom Composition ◽  
Putative Toxin

Ontogenetic changes in venom composition have been described in Bothrops snakes, but only a few studies have attempted to identify the targeted paralogues or the molecular mechanisms involved in modifications of gene expression during ontogeny. In this study, we decoded B. jararacussu venom gland transcripts from six specimens of varying sizes and analyzed the variability in the composition of independent venom proteomes from 19 individuals. We identified 125 distinct putative toxin transcripts, and of these, 73 were detected in venom proteomes and only 10 were involved in the ontogenetic changes. Ontogenetic variability was linearly related to snake size and did not correspond to the maturation of the reproductive stage. Changes in the transcriptome were highly predictive of changes in the venom proteome. The basic myotoxic phospholipases A2 (PLA2s) were the most abundant components in larger snakes, while in venoms from smaller snakes, PIII-class SVMPs were the major components. The snake venom metalloproteinases (SVMPs) identified corresponded to novel sequences and conferred higher pro-coagulant and hemorrhagic functions to the venom of small snakes. The mechanisms modulating venom variability are predominantly related to transcriptional events and may consist of an advantage of higher hematotoxicity and more efficient predatory function in the venom from small snakes.

scholarly journals The molecular basis, genetic control and pleiotropic effects of local gene co-expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diogo M. Ribeiro ◽  
Simone Rubinacci ◽  
Anna Ramisch ◽  
Robin J. Hofmeister ◽  
Emmanouil T. Dermitzakis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Control ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Gene Interactions ◽  
Human Tissues ◽  
Public Database ◽  
Functional Interpretation ◽  
Molecular Assays ◽  
Gene Pairs

AbstractNearby genes are often expressed as a group. Yet, the prevalence, molecular mechanisms and genetic control of local gene co-expression are far from being understood. Here, by leveraging gene expression measurements across 49 human tissues and hundreds of individuals, we find that local gene co-expression occurs in 13% to 53% of genes per tissue. By integrating various molecular assays (e.g. ChIP-seq and Hi-C), we estimate the ability of several mechanisms, such as enhancer-gene interactions, in distinguishing gene pairs that are co-expressed from those that are not. Notably, we identify 32,636 expression quantitative trait loci (eQTLs) which associate with co-expressed gene pairs and often overlap enhancer regions. Due to affecting several genes, these eQTLs are more often associated with multiple human traits than other eQTLs. Our study paves the way to comprehend trait pleiotropy and functional interpretation of QTL and GWAS findings. All local gene co-expression identified here is available through a public database (https://glcoex.unil.ch/).

scholarly journals The Study of Cerebrospinal Fluid microRNAs in Spinal Cord Injury and Neurodegenerative Diseases: Methodological Problems and Possible Solutions

2021 ◽  
Vol 23 (1) ◽  
pp. 114
Author(s):  
Irina Baichurina ◽  
Victor Valiullin ◽  
Victoria James ◽  
Albert Rizvanov ◽  
Yana Mukhamedshina
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Rna Isolation ◽  
Cord Injury

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions.

Identification of early gene expression changes during human Th17 cell differentiation

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. e151-e160 ◽  
Author(s):  
Soile Tuomela ◽  
Verna Salo ◽  
Subhash K. Tripathi ◽  
Zhi Chen ◽  
Kirsti Laurila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Th17 Cell ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Early Gene ◽  
Th17 Cell Differentiation ◽  
Genome Wide ◽  
Starting Point ◽  
Th17 Differentiation

Abstract Th17 cells play an essential role in the pathogenesis of autoimmune and inflammatory diseases. Most of our current understanding on Th17 cell differentiation relies on studies carried out in mice, whereas the molecular mechanisms controlling human Th17 cell differentiation are less well defined. In this study, we identified gene expression changes characterizing early stages of human Th17 cell differentiation through genome-wide gene expression profiling. CD4+ cells isolated from umbilical cord blood were used to determine detailed kinetics of gene expression after initiation of Th17 differentiation with IL1β, IL6, and TGFβ. The differential expression of selected candidate genes was further validated at protein level and analyzed for specificity in initiation of Th17 compared with initiation of other Th subsets, namely Th1, Th2, and iTreg. This first genome-wide profiling of transcriptomics during the induction of human Th17 differentiation provides a starting point for defining gene regulatory networks and identifying new candidates regulating Th17 differentiation in humans.

Global Gene Expression Analysis of Rodent Motor Neurons Following Spinal Cord Injury Associates Molecular Mechanisms With Development of Postinjury Spasticity

2010 ◽  
Vol 103 (2) ◽  
pp. 761-778 ◽  
Author(s):  
J. Wienecke ◽  
A-C. Westerdahl ◽  
H. Hultborn ◽  
O. Kiehn ◽  
J. Ryge
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Global Gene Expression ◽  
Motor Dysfunction ◽  
Plateau Potentials ◽  
Endogenous Expression ◽  
Cord Injury

Spinal cord injury leads to severe problems involving impaired motor, sensory, and autonomic functions. After spinal injury there is an initial phase of hyporeflexia followed by hyperreflexia, often referred to as spasticity. Previous studies have suggested a relationship between the reappearance of endogenous plateau potentials in motor neurons and the development of spasticity after spinalization. To unravel the molecular mechanisms underlying the increased excitability of motor neurons and the return of plateau potentials below a spinal cord injury we investigated changes in gene expression in this cell population. We adopted a rat tail-spasticity model with a caudal spinal transection that causes a progressive development of spasticity from its onset after 2 to 3 wk until 2 mo postinjury. Gene expression changes of fluorescently identified tail motor neurons were studied 21 and 60 days postinjury. The motor neurons undergo substantial transcriptional regulation in response to injury. The patterns of differential expression show similarities at both time points, although there are 20% more differentially expressed genes 60 days compared with 21 days postinjury. The study identifies targets of regulation relating to both ion channels and receptors implicated in the endogenous expression of plateaux. The regulation of excitatory and inhibitory signal transduction indicates a shift in the balance toward increased excitability, where the glutamatergic N-methyl-d-aspartate receptor complex together with cholinergic system is up-regulated and the γ-aminobutyric acid type A receptor system is down-regulated. The genes of the pore-forming proteins Cav1.3 and Nav1.6 were not up-regulated, whereas genes of proteins such as nonpore-forming subunits and intracellular pathways known to modulate receptor and channel trafficking, kinetics, and conductivity showed marked regulation. On the basis of the identified changes in global gene expression in motor neurons, the present investigation opens up for new potential targets for treatment of motor dysfunction following spinal cord injury.

scholarly journals Author response: Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries

2017 ◽  
Author(s):  
Sebastian Ocklenburg ◽  
Judith Schmitz ◽  
Zahra Moinfar ◽  
Dirk Moser ◽  
Rena Klose ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Author Response ◽  
Hemispheric Asymmetries

scholarly journals The role of epigenetic regulation in adaptive phenotypic plasticity of plants

2021 ◽  
Vol 78 (5) ◽  
pp. 347-359
Author(s):  
E.L. Kordyum ◽  
◽  
D.V. Dubyna ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Phenotypic Plasticity ◽  
Epigenetic Regulation ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Model Species ◽  
Wide Range ◽  
Adaptive Phenotypic Plasticity

In recent decades, knowledge about the role of epigenetic regulation of gene expression in plant responses to external stimuli and in adaptation of plants to adverse environmental fluctuations have extended significantly. DNA methylation is considered as the main molecular mechanism that provides genomic information and contributes to the understanding of the molecular basis of phenotypic variations based on epigenetic modifications. Unfortunately, the vast majority of research in this area has been performed on the model species Arabidopsis thaliana. The development of the methylation-sensitive amplified polymorphism (MSAP) method has made it possible to implement the large-scale detection of DNA methylation alterations in wild non-model and agricultural plants with large and highly repetitive genomes in natural and manipulated habitats. The article presents current information on DNA methylation in species of natural communities and crops and its importance in plant development and adaptive phenotypic plasticity, along with brief reviews of current ideas about adaptive phenotypic plasticity and epigenetic regulation of gene expression. The great potential of further studies of the epigenetic role in phenotypic plasticity of a wide range of non-model species in natural populations and agrocenoses for understanding the molecular mechanisms of plant existence in the changing environment in onto- and phylogeny, directly related to the key tasks of forecasting the effects of global warming and crop selection, is emphasized. Specific taxa of the Ukrainian flora, which, in authors’ opinion, are promising and interesting for this type of research, are recommended.

scholarly journals The European Map Butterfly Araschnia levana as a Model to Study the Molecular Basis and Evolutionary Ecology of Seasonal Polyphenism

Insects ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 325
Author(s):  
Arne Baudach ◽  
Andreas Vilcinskas
Keyword(s):  
Gene Expression ◽  
Environmental Factors ◽  
Epigenetic Regulation ◽  
Molecular Basis ◽  
Evolutionary Ecology ◽  
Hormonal Control ◽  
Day Length ◽  
Seasonal Polyphenism ◽  
Developmental Fate ◽  
Ecological Parameters

The European map butterfly Araschnia levana is a well-known example of seasonal polyphenism. Spring and summer imagoes exhibit distinct morphological phenotypes. Key environmental factors responsible for the expression of different morphs are day length and temperature. Larval exposure to light for more than 16 h per day entails direct development and results in the adult f. prorsa summer phenotype. Less than 15.5 h per day increasingly promotes diapause and the adult f. levana spring phenotype. The phenotype depends on the timing of the release of 20-hydroxyecdysone in pupae. Release within the first days after pupation potentially inhibits the default “levana-gene-expression-profile” because pre-pupae destined for diapause or subitaneous development have unique transcriptomic programs. Moreover, multiple microRNAs and their targets are differentially regulated during the larval and pupal stages, and candidates for diapause maintenance, duration, and phenotype determination have been identified. However, the complete pathway from photoreception to timekeeping and diapause or subitaneous development remains unclear. Beside the wing polyphenism, the hormonal and epigenetic modifications of the two phenotypes also include differences in biomechanical design and immunocompetence. Here, we discuss research on the physiological and molecular basis of polyphenism in A. levana, including hormonal control, epigenetic regulation, and the effect of ecological parameters on developmental fate.

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