scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

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.

scholarly journals Genome-Wide Expression and Alternative Splicing in Domesticated Sunflowers (Helianthus annuus L.) under Flooding Stress

Agronomy ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 92
Author(s):  
Joon Seon Lee ◽  
Lexuan Gao ◽  
Laura Melissa Guzman ◽  
Loren H. Rieseberg
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Mixed Model ◽  
Agricultural Land ◽  
Alcohol Fermentation ◽  
Expression Levels ◽  
Flooding Stress ◽  
Genome Wide ◽  
And Control ◽  
Gene Expression Levels

Approximately 10% of agricultural land is subject to periodic flooding, which reduces the growth, survivorship, and yield of most crops, reinforcing the need to understand and enhance flooding resistance in our crops. Here, we generated RNA-Seq data from leaf and root tissue of domesticated sunflower to explore differences in gene expression and alternative splicing (AS) between a resistant and susceptible cultivar under both flooding and control conditions and at three time points. Using a combination of mixed model and gene co-expression analyses, we were able to separate general responses of sunflower to flooding stress from those that contribute to the greater tolerance of the resistant line. Both cultivars responded to flooding stress by upregulating expression levels of known submergence responsive genes, such as alcohol dehydrogenases, and slowing metabolism-related activities. Differential AS reinforced expression differences, with reduced AS frequencies typically observed for genes with upregulated expression. Significant differences were found between the genotypes, including earlier and stronger upregulation of the alcohol fermentation pathway and a more rapid return to pre-flooding gene expression levels in the resistant genotype. Our results show how changes in the timing of gene expression following both the induction of flooding and release from flooding stress contribute to increased flooding tolerance.

Mammalian genome evolution as a result of epigenetic regulation of transposable elements

2014 ◽  
Vol 5 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Reuben M. Buckley ◽  
David L. Adelson
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Epigenetic Regulation ◽  
Dna Sequences ◽  
Defense Mechanisms ◽  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Epigenetic Marks ◽  
Rna Molecules ◽  
Mammalian Genomes

AbstractTransposable elements (TEs) make up a large proportion of mammalian genomes and are a strong evolutionary force capable of rewiring regulatory networks and causing genome rearrangements. Additionally, there are many eukaryotic epigenetic defense mechanisms able to transcriptionally silence TEs. Furthermore, small RNA molecules that target TE DNA sequences often mediate these epigenetic defense mechanisms. As a result, epigenetic marks associated with TE silencing can be reestablished after epigenetic reprogramming – an event during the mammalian life cycle that results in widespread loss of parental epigenetic marks. Furthermore, targeted epigenetic marks associated with TE silencing may have an impact on nearby gene expression. Therefore, TEs may have driven species evolution via their ability to heritably alter the epigenetic regulation of gene expression in mammals.

scholarly journals Diurnal.plant.tools: comparative transcriptomic and co-expression analyses of diurnal gene expression of the Archaeplastida kingdom

2019 ◽  
Author(s):  
Jonathan Wei Xiong Ng ◽  
Qiao Wen Tan ◽  
Camilla Ferrari ◽  
Marek Mutwil
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Species Comparisons ◽  
Gene Modules ◽  
Time Specific ◽  
Almost All ◽  
User Friendly ◽  
Diurnal Regulation

ABSTRACTAlmost all organisms coordinate some aspects of their biology through the diurnal cycle. Photosynthetic organisms, and plants especially, have established complex programs that coordinate physiological, metabolic and developmental processes with the changing light. The diurnal regulation of the underlying transcriptional processes is observed when groups of functionally related genes (gene modules) are expressed at a specific time of the day. However, studying the diurnal regulation of these gene modules in the plant kingdom was hampered by the large amount of data required for the analyses. To meet this need, we used gene expression data from 17 diurnal studies spanning the whole Archaeplastida kingdom (Plantae kingdom in the broad sense) to make an online diurnal database. We have equipped the database with tools that allow user-friendly cross-species comparisons of gene expression profiles, entire co-expression networks, co-expressed clusters (involved in specific biological processes), time-specific gene expression, and others. We exemplify how these tools can be used by studying three important biological questions: (i) the evolution of cell division, (ii) the diurnal control of gene modules in algae and (iii) the conservation of diurnally-controlled modules across species. The database is freely available at http://diurnal.plant.tools/.

scholarly journals Gene expression levels of DNA methyltransferase enzymes in Shank3-deficient mouse model of autism during early development

2021 ◽  
Vol 55 (4) ◽  
pp. 234-237
Author(s):  
Annamaria Srancikova ◽  
Alexandra Reichova ◽  
Zuzana Bacova ◽  
Jan Bakos
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Brain Development ◽  
Early Development ◽  
Molecular Mechanisms ◽  
Altered Expression ◽  
Expression Levels ◽  
The Brain ◽  
Deficient Mice ◽  
Gene Expression Levels

Abstract Objectives. The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 (Shank3)-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms. DNA methyltransferases (DNMTs), which modulate several cellular processes in neurodevelopment, are implicated in the pathophysiology of autism. In this study, we aimed to describe the gene expression changes of major Dnmts in the brain of Shank3-deficient mice during early development. Methods and Results. The Dnmts gene expression was analyzed by qPCR in 5-day-old homo-zygous Shank3-deficient mice. We found significantly lower Dnmt1 and Dnmt3b gene expression levels in the frontal cortex. However, no such changes were observed in the hippocampus. However, significant increase was observed in the expression of Dnmt3a and Dnmt3b genes in the hypothalamus of Shank3-deficient mice. Conclusions. The present data indicate that abnormalities in the Shank3 gene are accompanied by an altered expression of DNA methylation enzymes in the early brain development stages, therefore, specific epigenetic control mechanisms in autism-relevant models should be more extensively investigated.

Abstract 312: Transcriptional and Posttranscriptional Circuitry in the Brain After Transient and Permanent Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Fatiha Tabet ◽  
Sandy Lee ◽  
Luisa F Cuesta Torres ◽  
Michael G Levin ◽  
Grant R Drummond ◽  
...  
Keyword(s):  
Gene Expression ◽  
Validation Studies ◽  
Regulatory Networks ◽  
Functional Roles ◽  
Sham Procedure ◽  
Gene Regulatory ◽  
Neurological Processes ◽  
The Brain

Background: Stroke is a major neurovascular disease and a leading cause of mortality and long-term disability. Within cells of the brain, short non-encoding microRNAs (miRNAs) serve to modulate gene expression and likely contribute to most, neurological processes. However, miRNA changes in the brain tissue in response to stroke have not been reported. Aim: To investigate the functional roles of brain miRNAs and gene regulatory networks in stroke injury. Methods: Adult (8-12 weeks old) male C57Bl/6 mice underwent intraluminal filament-induced middle cerebral artery (MCA) occlusion. Permanent ischemia (ischemia no reperfusion, InoR; n=8) was achieved by occlusion for 24 h, and ischemia with reperfusion (IR; n=8) was completed after 30 min of MCA followed by 23.5 h of reperfusion. Sham-operated mice (n=8) were used as controls. Total RNA was isolated from mouse brains and gene arrays (Affymetrix) and miRNA arrays (TaqMan OpenArray microRNA) were performed. Validation studies were performed using RT-PCR and TaqMan Individual Assays. Results: Relative to the sham-operated mice, InoR significantly altered (p≤0.05; fold-change≥1.5) the levels of 471 genes (mRNA) in the brain. By contrast, IR resulted in only 114 significant changes in gene expression after 24 h. Brain miRNAs were also very sensitive to both ischemia and reperfusion. 28 miRNAs (11 down, 17 up) were significantly altered by InoR compared to the sham procedure. Likewise, 12 miRNAs (3 down, 9 up) were significantly altered with reperfusion compared to the sham procedure. Interestingly, we found 10 miRNAs to be significantly altered (5 up, 5 down) with ischemia (InoR/Sham), but were also significantly corrected towards normal Sham levels by 23.5 h reperfusion (IR/InoR). Validation studies confirmed that levels of multiple miRNAs were significantly altered with InoR. Reperfusion increased the levels of all these miRNAs. 48% (327/680) of the mRNAs that were altered were predicted targets of significantly altered miRNAs, and our results showed inverse directional changes. Conclusion: Results from our study show the role of miRNAs and post-transcriptional circuits in both adaptive and maladaptive responses to ischemic stroke and reperfusion.

scholarly journals Alternative splicing landscape of the neural transcriptome in a cytoplasmic-predominant Pten expression murine model of autism-like Behavior

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Stetson Thacker ◽  
Marilyn Sefyi ◽  
Charis Eng
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Murine Model ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Splicing Factors ◽  
Sequencing Data ◽  
Central Nervous Systems ◽  
Functional Complexity ◽  
The Brain

Abstract Alternative splicing (AS) is a posttranscriptional mechanism regulating gene expression that complex organisms utilize to expand proteome diversity from a comparatively limited set of genes. Recent research has increasingly associated AS with increased functional complexity in the central nervous systems in higher order mammals. This work has heavily implicated aberrant AS in several neurocognitive and neurodevelopmental disorders, including autism. Due to the strong genetic association between germline PTEN mutations and autism spectrum disorder (ASD), we hypothesized that germline PTEN mutations would alter AS patterns, contributing to the pathophysiology of ASD. In a murine model of constitutional mislocalization of Pten, recapitulating an autism-like phenotype, we found significant changes in AS patterns across the neural transcriptome by analyzing RNA-sequencing data with the program rMATS. A few hundred significant alternative splicing events (ASEs) that differentiate each m3m4 genotype were identified. These ASEs occur in genes enriched in PTEN signaling, inositol metabolism, and several other pathways relevant to the pathophysiology of ASD. In addition, we identified expression changes in several splicing factors known to be enriched in the nervous system. For instance, the master regulator of microexons, Srrm4, has decreased expression, and consequently, we found decreased inclusion of microexons in the Ptenm3m4/m3m4 cortex (~10% decrease). We also demonstrated that the m3m4 mutation disrupts the interaction between Pten and U2af2, a member of the spliceosome. In sum, our observations point to germline Pten disruption changing the landscape of alternative splicing in the brain, and these changes may be relevant to the pathogenesis and/or maintenance of PTEN-ASD phenotypes.

Effect of a thymol application on olfactory memory and gene expression levels in the brain of the honeybee Apis mellifera

2014 ◽  
Vol 22 (11) ◽  
pp. 8022-8030 ◽  
Author(s):  
Elsa Bonnafé ◽  
Florian Drouard ◽  
Lucie Hotier ◽  
Jean-Luc Carayon ◽  
Pierre Marty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Apis Mellifera ◽  
Olfactory Memory ◽  
Expression Levels ◽  
The Brain ◽  
Gene Expression Levels

scholarly journals Single-Cell Analysis of Alternative Splicing and Gene Regulatory Network Reveals Remarkable Expression and Regulation Dynamics During Early Embryonic Development

2021 ◽  
Author(s):  
Jiwei Chen ◽  
Yunjin Li ◽  
Geng Chen ◽  
Tieliu Shi
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Embryonic Development ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Early Embryonic Development ◽  
Expression Level ◽  
Specific Gene ◽  
Isoform Switching ◽  
Gene Regulatory

Abstract BackgroundSingle-cell RNA-seq (scRNA-seq) technologies greatly revolutionized our understanding of cell-to-cell variability of gene expression. Although several studies investigated the expression profile of early embryos, they mainly focused on the expression changes at gene level. Here we systematically explored the gene expression dynamics of human early embryonic development from expression level, alternative splicing, isoform switching and expression regulatory network. ResultsWe found that the genes involved in significant changes of these three aspects are all gradually decreased along embryonic development from E3 to E7 stage. Moreover, these three types of variations are complementary for profiling expression dynamics and they vary greatly across embryonic development as well as between different sexes. Strikingly, only a small number of genes exhibited prominent expression level changes between male and female embryos in E3 stage, whereas many more genes showed variations in alternative splicing and major isoform switching. Additionally, we identified functionally important specific gene regulatory modules for each stage and revealed dynamic usage of transcription factor binding motifs (TFBMs). ConclusionsCollectively, our study gain insights into the expression dynamics of early embryonic development from expression level, alternative splicing, isoform switching and gene regulatory networks, which could benefit the understanding of underlying mechanism of embryonic development.

scholarly journals Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells

Science ◽  
2021 ◽  
pp. eabg4696
Author(s):  
Ioannis Sarropoulos ◽  
Mari Sepp ◽  
Robert Frömel ◽  
Kevin Leiss ◽  
Nils Trost ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Organ Development ◽  
Development And Differentiation ◽  
Cerebellar Cell ◽  
Time Specific ◽  
Cerebellar Cells

Organ development is orchestrated by cell- and time-specific gene regulatory networks. In this study, we investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood. By acquiring snATAC-seq profiles for ~90,000 cells spanning eleven stages, we mapped cerebellar cell types and identified candidate cis-regulatory elements (CREs). We detected extensive spatiotemporal heterogeneity among progenitor cells and a gradual divergence in the regulatory programs of cerebellar neurons during differentiation. Comparisons to vertebrate genomes and snATAC-seq profiles for ∼20,000 cerebellar cells from the marsupial opossum revealed a shared decrease in CRE conservation during development and differentiation, but also differences in constraint between cell types. Our work delineates the developmental and evolutionary dynamics of gene regulation in cerebellar cells and provides insights into mammalian organ development.

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