Developmental series of gene expression clarifies maternal mRNA provisioning and maternal-to-zygotic transition in a reef-building coral

Abstract Background Maternal mRNA provisioning of oocytes regulates early embryogenesis. Maternal transcripts are degraded as zygotic genome activation (ZGA) intensifies, a phenomenon known as the maternal-to-zygotic transition (MZT). Here, we examine gene expression over nine developmental stages in the Pacific rice coral, Montipora capitata, from eggs and embryos at 1, 4, 9, 14, 22, and 36 h-post-fertilization (hpf), as well as swimming larvae (9d), and adult colonies. Results Weighted Gene Coexpression Network Analysis revealed four expression peaks, identifying the maternal complement, two waves of the MZT, and adult expression. Gene ontology enrichment revealed maternal mRNAs are dominated by cell division, methylation, biosynthesis, metabolism, and protein/RNA processing and transport functions. The first MZT wave occurs from ~4-14 hpf and is enriched in terms related to biosynthesis, methylation, cell division, and transcription. In contrast, functional enrichment in the second MZT wave, or ZGA, from 22 hpf-9dpf, includes ion/peptide transport and cell signaling. Finally, adult expression is enriched for functions related to signaling, metabolism, and ion/peptide transport. Our proposed MZT timing is further supported by expression of enzymes involved in zygotic transcriptional repression (Kaiso) and activation (Sox2), which peak at 14 hpf and 22 hpf, respectively. Further, DNA methylation writing (DNMT3a) and removing (TET1) enzymes peak and remain stable past ~4 hpf, suggesting that methylome programming occurs before 4 hpf. Conclusions Our high-resolution insight into the coral maternal mRNA and MZT provides essential baseline information to understand parental carryover effects and the sensitivity of developmental success under increasing environmental stress.

Download Full-text

Developmental series of gene expression clarifies maternal mRNA provisioning and maternal-to-zygotic transition in the reef-building coral Montipora capitata

10.1101/2021.04.14.439692 ◽

2021 ◽

Author(s):

E Chille ◽

E Strand ◽

M Neder ◽

V Schmidt ◽

M Sherman ◽

...

Keyword(s):

Gene Expression ◽

Cell Division ◽

Transcriptional Repression ◽

Developmental Stages ◽

Functional Enrichment ◽

Peptide Transport ◽

Essential Information ◽

Montipora Capitata ◽

Maternal Mrna ◽

Maternal To Zygotic Transition

AbstractBackgroundMaternal mRNA provisioning of oocytes regulates early embryogenesis. Maternal transcripts are degraded as zygotic genome activation (ZGA) intensifies, a phenomenon known as the maternal-to-zygotic transition (MZT). Here, we examine gene expression over nine developmental stages in the Pacific rice coral, Montipora capitata, from eggs and embryos at 1, 4, 9, 14, 22, and 36 hours-post-fertilization (hpf), as well as swimming larvae (9d), and adult colonies.ResultsWeighted Gene Coexpression Network Analysis revealed four expression peaks, identifying the maternal complement, two waves of the MZT, and adult expression. Gene ontology enrichment revealed maternal mRNAs are dominated by cell division, methylation, biosynthesis, metabolism, and protein/RNA processing and transport functions. The first MZT wave occurs from ∼4-14 hpf and is enriched in terms related to biosynthesis, methylation, cell division, and transcription. In contrast, functional enrichment in the second MZT wave, or ZGA, from 22 hpf-9dpf, includes ion/peptide transport and cell signaling. Finally, adult expression is enriched for functions related to signaling, metabolism, and ion/peptide transport. Our proposed MZT timing is further supported by expression of enzymes involved in zygotic transcriptional repression (Kaiso) and activation (Sox2), which peak at 14 hpf and 22 hpf, respectively. Further, DNA methylation writing (DNMT3a) and removing enzymes (TET1) peak and remain stable past ∼4 hpf, indicating that methylome programming occurs before 4 hpf.ConclusionsOur high-resolution insight into the coral maternal mRNA and MZT provides essential information regarding setting the stage for, and the sensitivity of, developmental success and parental carryover effects under increasing environmental stress.

Download Full-text

Whi5 and Stb1 define redundant pathways through which the G1 cyclin Cln3 promotes cell division

10.1101/2021.11.04.467365 ◽

2021 ◽

Author(s):

Sangeet Honey ◽

Bruce Futcher

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Transcription Factors ◽

Cell Division ◽

Transcriptional Repression ◽

Phosphorylation Site ◽

Phosphorylation Sites ◽

G1 Cyclin ◽

Cdk Phosphorylation ◽

Commitment To Cell Division

In the budding yeast S. cerevisiae, commitment to cell division, Start, is promoted by a trio of G1 cyclins, Cln1, Cln2, and Cln3, that activate the CDK kinase Cdc28. The active kinases somehow activate two transcription factors, SBF and MBF, leading to induction of about 100 genes for budding, DNA synthesis, and other early cell cycle processes. Activation of the transcription factors is opposed by a repressive protein called Whi5, and also by a second repressive protein called Stb1. Both Whi5 and Stb1 contain many potential sites for phosphorylation by CDK kinase, and is thought that relief of transcriptional repression involves the phosphorylation of Whi5 and Stb1 by CDK. Phosphorylation site mutants have been studied for Whi5, but not for Stb1. Here, we create phosphorylation site mutants of Stb1, and combine them with site mutants of Whi5. We find that the G1 cyclin Cln3 activates cell cycle transcription effectively when at least one of these proteins has its phosphorylation sites. However, when both Whi5 and Stb1 simultaneously lack all consensus phosphorylation sites, Cln3 is unable, or almost unable, to induce any gene expression, or any advancement of Start. Thus the G1 cyclin signaling pathway to Start has a requirement for CDK phosphorylation sites on either Whi5 or Stb1.

Download Full-text

Sex differences in body composition, fat storage, and gene expression profile inCaenorhabditis elegansin response to dietary restriction

Physiological Genomics ◽

10.1152/physiolgenomics.00007.2013 ◽

2013 ◽

Vol 45 (13) ◽

pp. 539-551 ◽

Cited By ~ 6

Author(s):

Claudia Miersch ◽

Frank Döring

Keyword(s):

Gene Expression ◽

Body Composition ◽

Dietary Restriction ◽

Lipid Droplets ◽

Developmental Stages ◽

Model Organism ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Fat Free Mass ◽

Functional Enrichment

The metabolic and health-promoting effects of dietary restriction (DR) have been extensively studied in several species. The response to DR with respect to sex is essentially unknown. To address this question, we used the model organism Caenorhabditis elegans to analyze body composition and gene expression in males and hermaphrodites in response to DR. Unexpectedly, DR increased the fat-to-fat-free mass ratio and enlarged lipid droplets in both sexes to a similar extent. These effects were linked to a downregulation of the lipase-like 5 ( lipl-5) gene in both sexes at two developmental stages. By contrast, the reductions in body size, protein content, and total RNA content in response to DR were more pronounced in hermaphrodites than in males. Functional enrichment analysis of gene expression data showed a DR-induced downregulation of several embryogenesis-associated genes concomitant with an ongoing expression of sperm-associated genes in hermaphrodites. In conclusion, DR increases fat stores in both sexes of C. elegans in the form of large and possibly lipolysis-resistant lipid droplets and markedly alters the reproductive program in hermaphrodites but not in males.

Download Full-text

Identification of Hub Genes Associated With Immune Infiltration and Predict Prognosis in Hepatocellular Carcinoma via Bioinformatics Approaches

Frontiers in Genetics ◽

10.3389/fgene.2020.575762 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huaping Chen ◽

Junrong Wu ◽

Liuyi Lu ◽

Zuojian Hu ◽

Xi Li ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Cell Division ◽

Immune Cell ◽

Cox Regression ◽

Close Association ◽

Functional Enrichment ◽

Microtubule Assembly ◽

Hub Genes ◽

Immune Infiltration

AimsIn the cancer-related research field, there is currently a major need for a greater number of valuable biomarkers to predict the prognosis of hepatocellular carcinoma (HCC). In this study, we aimed to screen hub genes related to immune cell infiltration and explore their prognostic value for HCC.MethodsWe analyzed five datasets (GSE46408, GSE57957, GSE74656, GSE76427, and GSE87630) from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). A protein–protein interaction network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes; then, the hub genes were identified. Functional enrichment of the genes was performed on the Metascape website. Next, the expression of these hub genes was validated in several databases, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and Human Protein Atlas. We explored the correlations between the hub genes and infiltrated immune cells in the TIMER2.0 database. The survival curves were generated in GEPIA2, and the univariate and multivariate Cox regression analyses were performed using TIMER2.0.ResultsThe top ten hub genes [DNA topoisomerase II alpha (TOP2A), cyclin B2 (CCNB2), protein regulator of cytokinesis 1 (PRC1), Rac GTPase-activating protein 1 (RACGAP1), aurora kinase A (AURKA), cyclin-dependent kinase inhibitor 3 (CDKN3), nucleolar and spindle-associated protein 1 (NUSAP1), cell division cycle-associated 5 (CDCA5), abnormal spindle microtubule assembly (ASPM), and non-SMC condensin I complex subunit G (NCAPG)] were identified in subsequent analysis. These genes are most markedly enriched in cell division, suggesting their close association with tumorigenesis. Multi-database analyses validated that the hub genes were upregulated in HCC tissues. All hub genes positively correlated with several types of immune infiltration, including B cells, CD4+ T cells, macrophages, and dendritic cells. Furthermore, these hub genes served as independent prognostic factors, and the expression of these hub genes combing with the macrophage levels could help predict an unfavorable prognosis of HCC.ConclusionIn sum, these hub genes (TOP2A, CCNB2, PRC1, RACGAP1, AURKA, CDKN3, NUSAP1, CDCA5, ASPM, and NCAPG) may be pivotal markers for prognostic prediction as well as potentially work as targets for immune-based intervention strategies in HCC.

Download Full-text

A story of birth and death: mRNA translation and clearance at the onset of maternal-to-zygotic transition in mammals†

Biology of Reproduction ◽

10.1093/biolre/ioz012 ◽

2019 ◽

Vol 101 (3) ◽

pp. 579-590 ◽

Cited By ~ 21

Author(s):

Qian-Qian Sha ◽

Jue Zhang ◽

Heng-Yu Fan

Keyword(s):

Transcriptional Activation ◽

Translational Control ◽

De Novo ◽

Model Organism ◽

Mrna Translation ◽

Maternal Mrna ◽

Maternal To Zygotic Transition ◽

Maternal Transcripts ◽

Set Up ◽

Zygotic Genome

Abstract In mammals, maternal-to-zygotic transition (MZT), or oocyte-to-embryo transition, begins with oocyte meiotic resumption due to the sequential translational activation and destabilization of dormant maternal transcripts stored in the ooplasm. It then continues with the elimination of maternal transcripts during oocyte maturation and fertilization and ends with the full transcriptional activation of the zygotic genome during embryonic development. A hallmark of MZT in mammals is its reliance on translation and the utilization of stored RNAs and proteins, rather than de novo transcription of genes, to sustain meiotic maturation and early development. Impaired maternal mRNA clearance at the onset of MZT prevents zygotic genome activation and causes early arrest of developing embryos. In this review, we discuss recent advances in our knowledge of the mechanisms whereby mRNA translation and degradation are controlled by cytoplasmic polyadenylation and deadenylation which set up the competence of maturing oocyte to accomplish MZT. The emphasis of this review is on the mouse as a model organism for mammals and BTG4 as a licensing factor of MZT under the translational control of the MAPK cascade.

Download Full-text

Integrative Modelling of Gene Expression and Digital Phenotypes to Describe Senescence in Wheat

Genes ◽

10.3390/genes12060909 ◽

2021 ◽

Vol 12 (6) ◽

pp. 909

Author(s):

Anyela Valentina Camargo Rodriguez

Keyword(s):

Gene Expression ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Developmental Stages ◽

Computational Modelling ◽

Plant Morphology ◽

Reproductive Organs ◽

Biological Trait ◽

Cereal Grain ◽

Plant Level

Senescence is the final stage of leaf development and is critical for plants’ fitness as nutrient relocation from leaves to reproductive organs takes place. Although senescence is key in nutrient relocation and yield determination in cereal grain production, there is limited understanding of the genetic and molecular mechanisms that control it in major staple crops such as wheat. Senescence is a highly orchestrated continuum of interacting pathways throughout the lifecycle of a plant. Levels of gene expression, morphogenesis, and phenotypic development all play key roles. Yet, most studies focus on a short window immediately after anthesis. This approach clearly leaves out key components controlling the activation, development, and modulation of the senescence pathway before anthesis, as well as during the later developmental stages, during which grain development continues. Here, a computational multiscale modelling approach integrates multi-omics developmental data to attempt to simulate senescence at the molecular and plant level. To recreate the senescence process in wheat, core principles were borrowed from Arabidopsis Thaliana, a more widely researched plant model. The resulted model describes temporal gene regulatory networks and their effect on plant morphology leading to senescence. Digital phenotypes generated from images using a phenomics platform were used to capture the dynamics of plant development. This work provides the basis for the application of computational modelling to advance understanding of the complex biological trait senescence. This supports the development of a predictive framework enabling its prediction in changing or extreme environmental conditions, with a view to targeted selection for optimal lifecycle duration for improving resilience to climate change.

Download Full-text

Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach

BMC Gastroenterology ◽

10.1186/s12876-021-01626-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhongyuan Lin ◽

Yimin Wang ◽

Shiqing Lin ◽

Decheng Liu ◽

Guohui Mo ◽

...

Keyword(s):

Gene Expression ◽

Irritable Bowel Syndrome ◽

Abdominal Pain ◽

Gastrointestinal Disease ◽

Rectal Mucosa ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Irritable Bowel ◽

Potential Biomarkers

Abstract Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS. Methods Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database. Fifty-three rectal mucosa samples from 27 irritable bowel syndrome with diarrhea (IBS-D) patients and 40 samples from 21 healthy volunteers as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein–protein interaction network was constructed and visualized using STRING database and Cytoscape. Results The microarray analysis demonstrated a subset of genes (CCKBR, CCL13, ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients. Conclusions Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.

Download Full-text

Spatio-temporal selection of reference genes in the two congeneric species of Glycyrrhiza

Scientific Reports ◽

10.1038/s41598-020-79298-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuping Li ◽

Xiaoju Liang ◽

Xuguo Zhou ◽

Yu An ◽

Ming Li ◽

...

Keyword(s):

Gene Expression ◽

Developmental Stage ◽

Reference Genes ◽

Developmental Stages ◽

Individual Factors ◽

Congeneric Species ◽

Spatio Temporal ◽

The Stability ◽

Different Tissues ◽

Selection Of

AbstractGlycyrrhiza, a genus of perennial medicinal herbs, has been traditionally used to treat human diseases, including respiratory disorders. Functional analysis of genes involved in the synthesis, accumulation, and degradation of bioactive compounds in these medicinal plants requires accurate measurement of their expression profiles. Reverse transcription quantitative real-time PCR (RT-qPCR) is a primary tool, which requires stably expressed reference genes to serve as the internal references to normalize the target gene expression. In this study, the stability of 14 candidate reference genes from the two congeneric species G. uralensis and G. inflata, including ACT, CAC, CYP, DNAJ, DREB, EF1, RAN, TIF1, TUB, UBC2, ABCC2, COPS3, CS, R3HDM2, were evaluated across different tissues and throughout various developmental stages. More importantly, we investigated the impact of interactions between tissue and developmental stage on the performance of candidate reference genes. Four algorithms, including geNorm, NormFinder, BestKeeper, and Delta Ct, were used to analyze the expression stability and RefFinder, a comprehensive software, provided the final recommendation. Based on previous research and our preliminary data, we hypothesized that internal references for spatio-temporal gene expression are different from the reference genes suited for individual factors. In G. uralensis, the top three most stable reference genes across different tissues were R3HDM2, CAC and TUB, while CAC, CYP and ABCC2 were most suited for different developmental stages. CAC is the only candidate recommended for both biotic factors, which is reflected in the stability ranking for the spatio (tissue)-temporal (developmental stage) interactions (CAC, R3HDM2 and DNAJ). Similarly, in G. inflata, COPS3, R3HDM2 and DREB were selected for tissues, while RAN, COPS3 and CS were recommended for developmental stages. For the tissue-developmental stage interactions, COPS3, DREB and ABCC2 were the most suited reference genes. In both species, only one of the top three candidates was shared between the individual factors and their interactions, specifically, CAC in G. uralensis and COPS3 in G. inflata, which supports our overarching hypothesis. In summary, spatio-temporal selection of reference genes not only lays the foundation for functional genomics research in Glycyrrhiza, but also facilitates these traditional medicinal herbs to reach/maximize their pharmaceutical potential.

Download Full-text

Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-021-00161-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Rowan AlEjielat ◽

Anas Khaleel ◽

Amneh H. Tarkhan

Keyword(s):

Gene Expression ◽

Ankylosing Spondylitis ◽

Differentially Expressed Genes ◽

Gene Network ◽

Disease Diagnosis ◽

Receptor Activation ◽

Functional Enrichment ◽

Differentially Expressed ◽

Inflammatory Disorder ◽

Data Set

Abstract Background Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogenesis have not been entirely identified. The current study aimed at constructing a gene network that may serve as an AS gene signature and biomarker, both of which will help in disease diagnosis and the identification of therapeutic targets. Previously published gene expression profiles of 16 AS patients and 16 gender- and age-matched controls that were profiled on the Illumina HumanHT-12 V3.0 Expression BeadChip platform were mined. Patients were Portuguese, 21 to 64 years old, were diagnosed based on the modified New York criteria, and had Bath Ankylosing Spondylitis Disease Activity Index scores > 4 and Bath Ankylosing Spondylitis Functional Index scores > 4. All patients were receiving only NSAIDs and/or sulphasalazine. Functional enrichment and pathway analysis were performed to create an interaction network of differentially expressed genes. Results ITM2A, ICOS, VSIG10L, CD59, TRAC, and CTLA-4 were among the significantly differentially expressed genes in AS, but the most significantly downregulated genes were the HLA-DRB6, HLA-DRB5, HLA-DRB4, HLA-DRB3, HLA-DRB1, HLA-DQB1, ITM2A, and CTLA-4 genes. The genes in this study were mostly associated with the regulation of the immune system processes, parts of cell membrane, and signaling related to T cell receptor and antigen receptor, in addition to some overlaps related to the IL2 STAT signaling, as well as the androgen response. The most significantly over-represented pathways in the data set were associated with the “RUNX1 and FOXP3 which control the development of regulatory T lymphocytes (Tregs)” and the “GABA receptor activation” pathways. Conclusions Comprehensive gene analysis of differentially expressed genes in AS reveals a significant gene network that is involved in a multitude of important immune and inflammatory pathways. These pathways and networks might serve as biomarkers for AS and can potentially help in diagnosing the disease and identifying future targets for treatment.

Download Full-text

975. Why Sex Make a Difference in HIV Clinical Course? Bioinformatics Analysis of Differential Expressed Gene in Females and Males with HIV Disease

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1161 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S516-S517

Author(s):

Kulachanya Suwanwongse ◽

Nehad Shabarek

Keyword(s):

Gene Expression ◽

Bioinformatics Analysis ◽

Underlying Mechanism ◽

Gene Expression Omnibus ◽

Functional Enrichment ◽

Gender Inequalities ◽

Hiv Disease ◽

Go Analysis ◽

Hiv Progression ◽

Pathway Analyses

Abstract Background Human immunodeficiency virus (HIV) disease progression are different among genders, in which women usually progress to acquired immunodeficiency syndrome (AIDS) faster than men. The mechanisms resulting in the gender biases of HIV progression are unclear. We conducted a bioinformatics analysis of differentially expressed genes (DEGs) in women and men with HIV disease to understand the sex-based differences in HIV pathogenesis. Methods We obtained microarray data from the Gene Expression Omnibus (GEO) database using our pre-defined search strategy and analyzed data using the GEO2R platform. The t-test was done to compare DEGs between females and males with HIV diseases. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was implemented to systematically extract biological features and processes of retrieving DEGs via gene ontology (GO) analysis. A Systemic search was performed to evaluate each DEG function and its possible association with HIV. Results One gene expression profiling data were retrieved: GSE 140713, composed of 40 males and 10 females with HIV1 infected samples. A GEO2R analysis yielded 19 DEGs (Table 1). The GO analysis result was demonstrated in Tables 2 and 3. Following a systemic search, we found two DEGs, which have previous studies reported an association with HIV: DDX3X (20 studies) and PDS5 (1 study). We proposed DDX3X (t 5.3, p 0.0037) is responsible for gender inequalities of HIV progression because of: 1. DDX3X is needed in the HIV1 life cycle. 2. Several studies confirmed a positive correlation between DDX3X expression and HIV1 replication. 3. Our study found an up-regulated DDX3X expression in women corresponded to the fact that women progress to AIDS faster than men. 4. Our GO analysis showed female up-regulated genes were enriched in positive regulation of the gene expression pathway, which can be explained by DDX3X and its underlying mechanism. Table 1: DEGs in women and men with HIV1 disease Table 2: GO functional enrichment pathway analyses of overall retrieving DEGs Table 3: GO functional enrichment pathway analyses of down- and up-regulated clusters of DEGs Conclusion Aberrant DDX3X expression may contribute to sex-based differences in HIV disease. Drugs modifying DDX3X gene expression will be beneficial in the treatment of HIV especially resolving the HIV drug resistance problem because current anti-HIV drugs target viral components posed the risk of viral mutation. Disclosures All Authors: No reported disclosures

Download Full-text