Floral pathway integrator gene expression mediates gradual transmission of environmental and endogenous cues to flowering time

The appropriate timing of flowering is crucial for the reproductive success of plants. Hence, intricate genetic networks integrate various environmental and endogenous cues such as temperature or hormonal statues. These signals integrate into a network of floral pathway integrator genes. At a quantitative level, it is currently unclear how the impact of genetic variation in signaling pathways on flowering time is mediated by floral pathway integrator genes. Here, using datasets available from literature, we connect Arabidopsis thaliana flowering time in genetic backgrounds varying in upstream signalling components with the expression levels of floral pathway integrator genes in these genetic backgrounds. Our modelling results indicate that flowering time depends in a quite linear way on expression levels of floral pathway integrator genes. This gradual, proportional response of flowering time to upstream changes enables a gradual adaptation to changing environmental factors such as temperature and light.

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Floral pathway integrator gene expression mediates gradual transmission of environmental and endogenous cues to flowering time

10.7287/peerj.preprints.2724v1 ◽

2017 ◽

Author(s):

Aalt D.J. van Dijk ◽

Jaap Molenaar

Keyword(s):

Gene Expression ◽

Arabidopsis Thaliana ◽

Genetic Variation ◽

Reproductive Success ◽

Environmental Factors ◽

Flowering Time ◽

Genetic Networks ◽

Expression Levels ◽

Quantitative Level ◽

The Impact

The appropriate timing of flowering is crucial for the reproductive success of plants. Hence, intricate genetic networks integrate various environmental and endogenous cues such as temperature or hormonal statues. These signals integrate into a network of floral pathway integrator genes. At a quantitative level, it is currently unclear how the impact of genetic variation in signaling pathways on flowering time is mediated by floral pathway integrator genes. Here, using datasets available from literature, we connect Arabidopsis thaliana flowering time in genetic backgrounds varying in upstream signalling components with the expression levels of floral pathway integrator genes in these genetic backgrounds. Our modelling results indicate that flowering time depends in a quite linear way on expression levels of floral pathway integrator genes. This gradual, proportional response of flowering time to upstream changes enables a gradual adaptation to changing environmental factors such as temperature and light.

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Expression of mRNAs for Pro-and Anti-Apoptotic Factors in Granulosa Cells and Follicular Fluid of Women Undergoing in Vitro Fertilization. A Pilot Study

10.21203/rs.3.rs-330029/v1 ◽

2021 ◽

Author(s):

Jozsef Bodis ◽

Endre Sulyok ◽

Akos Varnagy ◽

Viktória Prémusz ◽

Krisztina Godony ◽

...

Keyword(s):

Gene Expression ◽

In Vitro Fertilization ◽

Mrna Expression ◽

Granulosa Cells ◽

Follicular Fluid ◽

Vitro Fertilization ◽

Expression Levels ◽

The Impact ◽

Apoptotic Factors

Abstract BackgroundThis observational clinical study evaluated the expression levels and predictive values of some apoptosis-related genes in granulosa cells (GCs) and follicular fluid (FF) of women undergoing in vitro fertilization (IVF).Methods GCs and FF were obtained at oocyte retrieval from 31 consecutive patients with heterogeneous infertility diagnosis (age: 34.3±5.8 years, body mass index: 24.02±3.12 kg/m2, duration of infertility: 4.2±2.1 years). mRNA expression of pro-apoptotic (BAX, CASP3, CASP8) and anti-apoptotic (BCL2, AMH, AMHR, FSHR, LHR, CYP19A1) factors was determined by quantitative RT-PCR using ROCHE LightCycler 480. Results No significant difference in GC or FF mRNA expression of pro- and anti-apoptotic factors could be demonstrated between IVF patients with (9 patients) or without (22 patients) clinical pregnancy. Each transcript investigated was detected in FF, but their levels were markedly reduced and independent of those in GCs. The number of retrieved oocytes was positively associated with GC AMHR (r=0.393, p=0.029), but the day of embryo transfer was negatively associated with GC LHR (r=-0.414, p=0.020) and GC FSHR transcripts (r=-0.535, p=0.002). When pregnancy positive group was analysed separately the impact of apoptosis- related gene expressions on some selected measures of IVF success could be observed. Strong positive relationship was found between gene expression levels of pro- and anti-apoptotic factors in GCs.ConclusionOur study provides only marginal evidences for the apoptosis dependence of IVF outcome and suggests that the apoptosis process induces adaptive increases of the anti-apoptotic gene expression to attenuate apoptosis and to protect cell survival.

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Codon usage is an important determinant of gene expression levels largely through its effects on transcription

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1606724113 ◽

2016 ◽

Vol 113 (41) ◽

pp. E6117-E6125 ◽

Cited By ~ 122

Author(s):

Zhipeng Zhou ◽

Yunkun Dang ◽

Mian Zhou ◽

Lin Li ◽

Chien-hung Yu ◽

...

Keyword(s):

Gene Expression ◽

Codon Usage ◽

Important Determinant ◽

Mrna Translation ◽

Mrna Levels ◽

Protein Coding ◽

Expression Levels ◽

Highly Expressed Genes ◽

The Impact ◽

Gene Expression Levels

Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora. Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels.

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Variation in the expression of a transmembrane protein influences cell growth in Arabidopsis thaliana petals by altering auxin responses

BMC Plant Biology ◽

10.1186/s12870-020-02698-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Charlotte N. Miller ◽

Jack Dumenil ◽

Fu Hao Lu ◽

Caroline Smith ◽

Neil McKenzie ◽

...

Keyword(s):

Gene Expression ◽

Arabidopsis Thaliana ◽

Genetic Variation ◽

Cell Growth ◽

Plant Growth ◽

Cell Size ◽

Natural Populations ◽

Organ Size ◽

Substantial Contribution ◽

Over Expression

Abstract Background The same species of plant can exhibit very diverse sizes and shapes of organs that are genetically determined. Characterising genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control. Results We screened a relatively well characterised collection of Arabidopsis thaliana accessions for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in the expression of a previously uncharacterised gene At4g16850 (named as KSK) had a substantial role on variation in organ size by influencing cell size. Over-expression of KSK led to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response to KSK over-expression. ANT expression was also reduced in KSK over-expression lines, consistent with altered floral identities. Auxin responses were reduced in KSK over-expressing cells, consistent with changes in auxin-responsive gene expression. KSK may therefore influence auxin responses during petal development. Conclusions Understanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations of Arabidopsis thaliana to identify sequence variation in a promoter region of Arabidopsis accessions that mediated differences in the expression of a previously uncharacterised membrane protein. This variation contributed to altered auxin responses and cell size during petal growth.

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Inference of genetic networks from time-series of gene expression levels using random forests

2017 IEEE Conference on Computational Intelligence in Bioinformatics and Computational Biology (CIBCB) ◽

10.1109/cibcb.2017.8058522 ◽

2017 ◽

Cited By ~ 1

Author(s):

Shuhei Kimura ◽

Masato Tokuhisa ◽

Mariko Okada-Hatakeyama

Keyword(s):

Gene Expression ◽

Time Series ◽

Random Forests ◽

Genetic Networks ◽

Expression Levels ◽

Gene Expression Levels

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Association of gene expressions of TOP2A, GGH, and PECAM1 with hematogenous, lymph-node, and peritoneal recurrence in patients with stage II/III gastric cancer enrolled in the ACTS-GC study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4019 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4019-4019

Author(s):

Masanori Terashima ◽

Wataru Ichikawa ◽

Atsushi Ochiai ◽

Koji Kitada ◽

Issei Kurahashi ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Lymph Node ◽

Peritoneal Recurrence ◽

Stage Ii ◽

Taqman Assay ◽

Primary Tumors ◽

Expression Levels ◽

Biomarker Analysis ◽

The Impact

4019 Background: Exploratory biomarker analysis was conducted to identify factors related to relapse sites in the ACTS-GC study, a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients (pts) with stage II/III gastric cancer. Methods: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 pts (78.3%), and 63 genes involved in pyrimidine metabolic pathway, growth factor signaling pathway, apoptosis, DNA repair, etc., were analyzed by quantitative RT-PCR after TaqMan assay-based pre-amplification. Gene expression levels were normalized to the geometric mean expressions of GAPDH, ACTB, and RPLP0, used as reference genes. The expression of each gene was categorized as lower or higher than the median value. The impact of gene expression on relapse site was analyzed using the 5-year relapse-free survival (RFS) data of the ACTS-GC. Results: Among the 829 pts, hematogenous, lymph-node, and peritoneal recurrence developed in 72, 105, and 138 pts, respectively. The hazard ratios (HR) (S-1 vs. surgery alone) were 0.79 (95%CI, 0.54-1.16) for hematogenous, 0.51 (95%CI, 0.31-0.82) for lymph-node, and 0.60 (95%CI, 0.42-0.84) for peritoneal recurrence. Among 63 screened genes, topoisomerase II alpha (TOP2A), gamma-glutamyl hydrolase (GGH), and platelet/endothelial cell adhesion molecule 1 (PECAM1) most strongly correlated with hematogenous, lymph-node, and peritoneal recurrence, respectively. Hematogenous RFS was significantly worse in TOP2A high pts than in low pts (HR, 2.35; 95% CI, 1.55-3.57). Lymph-node RFS was significantly worse in GGH high pts than in low pts (HR, 1.87; 95% CI, 1.13-3.08). Likewise, peritoneal RFS was significantly worse in PECAM1high pts than in low pts (HR, 2.37: 95% CI, 1.65-3.41). These factors were independent and stronger risk factors than tumor histological type on multivariate analysis. Conclusions: Expression levels of the TOP2A, GGH, and PECAM1 genes in primary tumors are respectively linked to high risks of hematogenous, lymph-node, and peritoneal recurrence in pts with stage II/III gastric cancer.

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Natural genetic variation in whole-genome expression in Arabidopsis thaliana: the impact of physiological QTL introgression

Molecular Ecology ◽

10.1111/j.1365-294x.2006.02774.x ◽

2006 ◽

Vol 15 (5) ◽

pp. 1351-1365 ◽

Cited By ~ 29

Author(s):

THOMAS E. JUENGER ◽

TIERNEY WAYNE ◽

SANDRA BOLES ◽

V. VAUGHAN SYMONDS ◽

JOHN MCKAY ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Genetic Variation ◽

Whole Genome ◽

Natural Genetic Variation ◽

Genome Expression ◽

Whole Genome Expression ◽

The Impact ◽

Qtl Introgression

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Environmental perturbations lead to extensive directional shifts in RNA processing

10.1101/119974 ◽

2017 ◽

Author(s):

A. L. Richards ◽

D. Watza ◽

A. Findley ◽

A. Alazizi ◽

X. Wen ◽

...

Keyword(s):

Gene Expression ◽

Genetic Variation ◽

Rna Processing ◽

Complex Traits ◽

Intron Retention ◽

Vast Number ◽

Factor Binding ◽

Environmental Perturbations ◽

Exon Usage ◽

The Impact

AbstractEnvironmental perturbations have large effects on both organismal and cellular traits, including gene expression, but the extent to which the environment affects RNA processing remains largely uncharacterized. Recent studies have identified a large number of genetic variants associated with variation in RNA processing that also have an important role in complex traits; yet we do not know in which contexts the different underlying isoforms are used. Here, we comprehensively characterized changes in RNA processing events across 89 environments in five human cell types and identified 15,300 event shifts (FDR = 15%) comprised of eight event types in over 4,000 genes. Many of these changes occur consistently in the same direction across conditions, indicative of global regulation by trans factors. Accordingly, we demonstrate that environmental modulation of splicing factor binding predicts shifts in intron retention, and that binding of transcription factors predicts shifts in AFE usage in response to specific treatments. We validated the mechanism hypothesized for AFE in two independent datasets. Using ATAC-seq, we found altered binding of 64 factors in response to selenium at sites of AFE shift, including ELF2 and other factors in the ETS family. We also performed AFE QTL mapping in 373 individuals and found an enrichment for SNPs predicted to disrupt binding of the ELF2 factor. Together, these results demonstrate that RNA processing is dramatically changed in response to environmental perturbations through specific mechanisms regulated by trans factors.Author SummaryChanges in a cell’s environment and genetic variation have been shown to impact gene expression. Here, we demonstrate that environmental perturbations also lead to extensive changes in alternative RNA processing across a large number of cellular environments that we investigated. These changes often occur in a non-random manner. For example, many treatments lead to increased intron retention and usage of the downstream first exon. We also show that the changes to first exon usage are likely dependent on changes in transcription factor binding. We provide support for this hypothesis by considering how first exon usage is affected by disruption of binding due to treatment with selenium. We further validate the role of a specific factor by considering the effect of genetic variation in its binding sites on first exon usage. These results help to shed light on the vast number of changes that occur in response to environmental stimuli and will likely aid in understanding the impact of compounds to which we are daily exposed.

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Mutational Signatures as Sensors of Environmental Exposures: Role of Smoking in COVID-19 Vulnerabilities

10.1101/2021.09.27.461855 ◽

2021 ◽

Author(s):

Yoo-Ah Kim ◽

Ermin Hodzic ◽

Ariella Saslafsky ◽

Damian Wojtowicz ◽

Bayarbaatar Amgalan ◽

...

Keyword(s):

Gene Expression ◽

Environmental Factors ◽

Disease Progression ◽

Environmental Exposures ◽

Biological Processes ◽

Mutational Signatures ◽

Mutational Signature ◽

The Impact ◽

Pathway Level

Background: Environmental exposures such as smoking are widely recognized risk factors in the emergence of lung diseases such as lung cancer and acute respiratory distress syndrome (ARDS). However, the strength of environmental exposures is difficult to measure, making it challenging to understand their impacts. On the other hand, some COVID-19 patients develop ARDS in an unfavorable disease progression and smoking has been suggested as a potential risk factor among others. Yet initial studies on COVID-19 cases reported contradictory results on the effects of smoking on the disease. Some suggest that smoking might have a protective effect against it while other studies report an increased risk. A better understanding of how the exposure to smoking and other environmental factors affect biological processes relevant to SARS-CoV-2 infection and unfavorable disease progression is needed. Approach: In this study, we utilize mutational signatures associated with environmental factors as sensors of their exposure level. Many environmental factors including smoking are mutagenic and leave characteristic patterns of mutations, called mutational signatures, in affected genomes. We postulated that analyzing mutational signatures, combined with gene expression, can shed light on the impact of the mutagenic environmental factors to the biological processes. In particular, we utilized mutational signatures from lung adenocarcinoma (LUAD) data set collected in TCGA to investigate the role of environmental factors in COVID-19 vulnerabilities. Integrating mutational signatures with gene expression in normal tissues and using a pathway level analysis, we examined how the exposure to smoking and other mutagenic environmental factors affects the infectivity of the virus and disease progression. Results: By delineating changes associated with smoking in pathway-level gene expression and cell type proportions, our study demonstrates that mutational signatures can be utilized to study the impact of exogenous mutagenic factors on them. Consistent with previous findings, our analysis showed that smoking mutational signature (SBS4) is associated with activation of cytokines mediated singling pathways, leading to inflammatory responses. Smoking related changes in cell composition were also observed, including the correlation of SBS4 with the expansion of goblet cells. On the other hand, increased basal cells and decreased ciliated cells in proportion were associated with the strength of a different mutational signature (SBS5), which is present abundantly but not exclusively in smokers. In addition, we found that smoking increases the expression levels of genes that are upregulated in severe COVID-19 cases. Jointly, these results suggest an unfavorable impact of smoking on the disease progression and also provide novel findings on how smoking impacts biological processes in lung.

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