scholarly journals Genome-wide methylation and expression analyses reveal the epigenetic landscape of immune-related diseases for tobacco smoking

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ying Mao ◽  
Peng Huang ◽  
Yan Wang ◽  
Maiqiu Wang ◽  
Ming D. Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cigarette Smoke ◽  
Tobacco Smoking ◽  
Molecular Mechanisms ◽  
Functional Enrichment ◽  
Chronic Obstructive ◽  
Rna Seq ◽  
Immune System Diseases ◽  
Genome Wide ◽  
A Genome

Abstract Background Smoking is a major causal risk factor for lung cancer, chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), and is the main preventable cause of deaths in the world. The components of cigarette smoke are involved in immune and inflammatory processes, which may increase the prevalence of cigarette smoke-related diseases. However, the underlying molecular mechanisms linking smoking and diseases have not been well explored. This study was aimed to depict a global map of DNA methylation and gene expression changes induced by tobacco smoking and to explore the molecular mechanisms between smoking and human diseases through whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq). Results We performed WGBS on 72 samples (36 smokers and 36 nonsmokers) and RNA-seq on 75 samples (38 smokers and 37 nonsmokers), and cytokine immunoassay on plasma from 22 males (9 smokers and 13 nonsmokers) who were recruited from the city of Jincheng in China. By comparing the data of the two groups, we discovered a genome-wide methylation landscape of differentially methylated regions (DMRs) associated with smoking. Functional enrichment analyses revealed that both smoking-related hyper-DMR genes (DMGs) and hypo-DMGs were related to synapse-related pathways, whereas the hypo-DMGs were specifically related to cancer and addiction. The differentially expressed genes (DEGs) revealed by RNA-seq analysis were significantly enriched in the “immunosuppression” pathway. Correlation analysis of DMRs with their corresponding gene expression showed that genes affected by tobacco smoking were mostly related to immune system diseases. Finally, by comparing cytokine concentrations between smokers and nonsmokers, we found that vascular endothelial growth factor (VEGF) was significantly upregulated in smokers. Conclusions In sum, we found that smoking-induced DMRs have different distribution patterns in hypermethylated and hypomethylated areas between smokers and nonsmokers. We further identified and verified smoking-related DMGs and DEGs through multi-omics integration analysis of DNA methylome and transcriptome data. These findings provide us a comprehensive genomic map of the molecular changes induced by smoking which would enhance our understanding of the harms of smoking and its relationship with diseases.

scholarly journals Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family

2021 ◽  
Vol 17 ◽  
pp. 117693432110413
Author(s):  
Chaoxin Zhang ◽  
Tao Wang ◽  
Tongyan Cui ◽  
Shengwei Liu ◽  
Bing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phylogenetic Analysis ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Genome Wide ◽  
A Genome

The CCAAT/enhancer binding protein (C/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 C/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into 6 subgroups named C/EBPα, C/EBPβ, C/EBPδ, C/EBPε, C/EBPγ, and C/EBPζ. Gene expression analysis showed that the C/EBPα, C/EBPβ, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

scholarly journals Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression

2009 ◽  
Vol 296 (6) ◽  
pp. L888-L900 ◽  
Author(s):  
Tirumalai Rangasamy ◽  
Vikas Misra ◽  
Lijie Zhen ◽  
Clarke G. Tankersley ◽  
Rubin M. Tuder ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Phase I ◽  
Cigarette Smoke ◽  
Phase Ii ◽  
Pulmonary Emphysema ◽  
Molecular Mechanisms ◽  
The United States ◽  
Phase Iii ◽  
Chronic Obstructive

Cigarette smoking is the major risk factor for developing chronic obstructive pulmonary disease, the fourth leading cause of deaths in the United States. Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We used Affymetrix Gene Chip arrays to determine the temporal alterations in global gene expression during the progression of pulmonary emphysema in A/J mice. Chronic cigarette smoke (CS) exposure caused pulmonary emphysema in A/J mice, which was associated with pronounced bronchoalveolar inflammation, enhanced oxidative stress, and increased apoptosis of alveolar septal cells. Microarray analysis revealed the upregulation of 1,190, 715, 260, and 246 genes and the downregulation of 1,840, 730, 442, and 236 genes in the lungs of mice exposed to CS for 5 h, 8 days, and 1.5 and 6 mo, respectively. Most of the genes belong to the functional categories of phase I genes, Nrf2-regulated antioxidant and phase II genes, phase III detoxification genes, and others including immune/inflammatory response genes. Induction of the genes encoding multiple phase I enzymes was markedly higher in the emphysematous lungs, whereas reduced expression of various cytoprotective genes constituting ubiquitin-proteasome complex, cell survival pathways, solute carriers and transporters, transcription factors, and Nrf2-regulated antioxidant and phase II-responsive genes was noted. Our data indicate that the progression of CS-induced emphysema is associated with a steady decline in the expression of various genes involved in multiple pathways in the lungs of A/J mice. Many of the genes discovered in this study could rationally play an important role in the susceptibility to CS-induced emphysema.

scholarly journals iREAD: A Tool for Intron Retention Detection from RNA-seq Data

2017 ◽  
Author(s):  
Hong-Dong Li ◽  
Cory C. Funk ◽  
Nathan D. Price
Keyword(s):  
Intron Retention ◽  
Distribution Patterns ◽  
Functional Enrichment ◽  
Command Line ◽  
Rna Seq ◽  
Text File ◽  
Command Line Interface ◽  
Genome Wide ◽  
A Genome ◽  
Retained Introns

AbstractSummaryDetecting intron retention (IR) events is emerging as a specialized need for RNA-seq data analysis. Here we present iREAD (intron REtention Analysis and Detector), a tool to detect IR events genome-wide from high-throughput RNA-seq data. The command line interface for iREAD is implemented in Python. iREAD takes as input an existing BAM file, representing the transcriptome, and a text file containing the intron coordinates of a genome. It then 1) counts all reads that overlap intron regions, 2) detects IR vents by analyzing features of reads such as depth and distribution patterns, and 3) outputs a list of retained introns into a tab-delimited text file. The output can be directly used for further exploratory analysis such as differential intron expression and functional enrichment. iREAD provides a new and generic tool to interrogate poly-A enriched transcriptomic data of intron regions.Availabilitywww.libpls.net/[email protected]

scholarly journals Network analysis links genome-wide phenotypic and transcriptional stress responses in a bacterial pathogen with a large pan-genome

2016 ◽  
Author(s):  
Paul A. Jensen ◽  
Zeyu Zhu ◽  
Tim van Opijnen
Keyword(s):  
Gene Expression ◽  
Stress Responses ◽  
Meta Analysis ◽  
Bacterial Pathogen ◽  
Metabolic Model ◽  
Genetic Network ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome ◽  
Response To Stress

ABSTRACTBackgroundBacteria modulate subcellular processes to handle stressful environments. Genome-wide profiling of gene expression (RNA-Seq) and fitness (Tn-Seq) allows two views of the same genetic network underlying these responses. However, it remains unclear how they combine, enabling a bacterium to overcome a perturbation.ResultsHere we generate RNA-Seq and Tn-Seq profiles in three strains of S. pneumoniae in response to stress defined by different levels of nutrient depletion. These profiles show that genes that change their expression and/or become phenotypically important come from a diverse set of functional categories, and genes that are phenotypically important tend to be highly expressed. Surprisingly, we find that expression and fitness changes rarely occur on the same gene, which we confirmed by over 140 validation experiments. To rationalize these unexpected results we built the first genome-scale metabolic model of S. pneumoniae showing that differential expression and phenotypic importance actually correlate between nearest neighbors, although they are distinctly partitioned into small subnetworks. Moreover, a meta-analysis of 234 S. pneumoniae gene expression studies reveals that essential genes and phenotypically important subnetworks rarely change expression, indicating that they are shielded from transcriptional fluctuations and that a clear distinction exists between transcriptional and phenotypic response networks.ConclusionsWe present a genome-wide computational/experimental approach that contextualizes changes that occur on transcriptomic and phenomic levels in response to stress. Importantly, this highlights the need to connect disparate response networks, for instance in antibiotic target identification, where preferred targets are phenotypically important genes that would be overlooked by transcriptomic analyses alone.

cDNA Microarrays - Providing Insight into Organism/Chemotherapeutic Interactions

2010 ◽  
Vol 63 (8) ◽  
pp. 1308
Author(s):  
Elise P. Wright
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Holistic Approach ◽  
Cdna Microarrays ◽  
Gene Expression Measurement ◽  
Genome Wide ◽  
A Genome ◽  
Expression Measurement ◽  
Insight Into

cDNA microarrays are a technique for interrogating gene expression responses to novel compounds, including chemotherapeutics. This holistic approach to gene expression measurement provides a genome wide appraisal of which molecular mechanisms are targeted by or associated with a drug.

scholarly journals Genome-wide analysis of transcriptional bursting-induced noise in mammalian cells

2019 ◽  
Author(s):  
Hiroshi Ochiai ◽  
Tetsutaro Hayashi ◽  
Mana Umeda ◽  
Mika Yoshimura ◽  
Akihito Harada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Transcription Elongation ◽  
Mapk Signaling ◽  
Kinetic Properties ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Transcriptional Bursting

AbstractTranscriptional bursting is stochastic activation and inactivation of promoters, leading to discontinuous production of mRNA, and is considered to be a contributing factor to cell-to-cell heterogeneity in gene expression. However, it remains elusive how the kinetic properties of transcriptional bursting (e.g., burst size, burst frequency, and noise induced by transcriptional bursting) are regulated in mammalian cells. In this study, we performed a genome-wide analysis of transcriptional bursting in mouse embryonic stem cells (mESCs) using single-cell RNA-sequencing. We found that the kinetics of transcriptional bursting was determined by a combination of promoter and gene body binding proteins, including polycomb repressive complex 2 and transcription elongation-related factors. Furthermore, large-scale CRISPR-Cas9-based screening and functional analysis revealed that the Akt/MAPK signaling pathway regulated bursting kinetics by modulating transcription elongation efficiency. These results uncover key molecular mechanisms underlying transcriptional bursting and cell-to-cell gene expression noise in mammalian cells.

Long-Lasting Dysregulation of the Hematopoietic Stem Cell Compartment in Obesity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 245-245
Author(s):  
Jung-Mi Lee ◽  
Bryan Goddard ◽  
Ashwini S. Hinge ◽  
Bruce J. Aronow ◽  
Nathan Salomonis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Molecular Mechanisms ◽  
Interferon Response ◽  
Compensatory Mechanisms ◽  
Hematopoietic Stem ◽  
Genome Wide ◽  
A Genome ◽  
The Impact

Abstract Obesity is a complex pathological state defined by the excessive accumulation of adipose tissue and an array of hormonal, immunological and metabolic dysregulations. As such, obesity is a systemic stress that directly affects numerous organs and tissues. Notably, obesity and its sequelae modulate the immune system and the hematopoietic activity in the bone marrow (BM). Not surprisingly, obesity is also a well-established risk factor for leukemia associated with increased incidence and poor prognosis. However, despite their clinical relevance, mechanisms by which obesity affects the hematopoietic system remain elusive. Particularly, the impact of obesity on the hematopoietic stem cell (HSC) compartment has not been described. Using genetic and dietary mouse models of obesity, we conducted a "HSC-centered study" to determine how obesity affects HSCs and how these cells develop specific compensatory mechanisms to respond to this environment. Although HSCs in an obese environment displayed limited phenotypic and functional perturbations at steady state, they showed an aberrant response to hematopoietic stresses. In serial competitive transplantation assays, obesity-primed HSCs (defined as Lin- Sca-1+ c-Kit+ CD48- CD150+) showed a higher level of engraftment than controls in primary recipient mice (control, 20.8% +/-6.2 vs obese, 45.5% +/-14.6, p=0.022) but a dramatically reduced level of engraftment in secondary recipient mice (control: 25.8% +/-14.0 vs obese: 5.4% +/-3.9, p=0.033). Interestingly, BM analysis of secondary recipients showed reduced chimerism in all hematopoietic compartments but not in the HSC compartment. Altogether these results uncovered a biphasic behavior of the obesity-primed HSCs, characterized by an excessive differentiation response followed by a functional decline in which HSCs self-renew but fail to produce downstream progenitors. To unveil the molecular mechanisms involved in this aberrant activity, we performed a genome-wide gene expression analysis on HSCs isolated from normal and obese mice. Although the phenotype observed upon serial transplantation partially mimics HSC aging, obesity-primed HSCs did not share the molecular signature of old HSCs. Furthermore, down-regulation of interferon response-related genes (e.g Irak4, Irf7, Ifi27) and stress response-related genes (e.g. Stip1, Cgrrf1) showed that, unlike what has been described for committed progenitors, HSCs do not elicit a dramatic response to the inflammatory environment associated with obesity. In contrast obesity leads to the activation of specific molecular programs in HSCs. Firstly, obesity-primed HSCs showed up-regulation of multiples genes involved in the phosphatidylinositol signaling pathway (e.g. Pi4ka, Pi4k2b, Pi3kap1, Pi3kip1). Phosphoflow cytometry analysis indicated that this gene expression pattern was associated with the constitutive activation of the protein kinase AKT. While AKT activation is linked to functional HSC exhaustion, obesity-primed HSCs appeared refractory to this signal, suggesting the existence of compensatory mechanisms that protect the integrity of the HSCs in an obese environment. In parallel, we found that the aberrant activity of the obesity-primed HSCs was correlated with an elevated expression of Gfi1, a transcription factor critical for HSC quiescence and differentiation. Interestingly, the 2-fold increase in Gfi1 expression (p<10-5) observed in obesity-primed HSCs was maintained after serial transplantations in normal recipient mice indicating that the obese environment was able to promote the selection of a stable molecular program in the HSC compartment. Consistent with this idea, single-cell genome-wide analyses suggested a significant clonal shift within the obesity-primed HSC compartment. Finally, consistent with epidemiological data, we found that disruption of HSC homeostasis by obesity promotes the development of spontaneous hematopoietic pathologies resembling to myeloproliferative diseases. Altogether, our results establish the long lasting impact of obesity on the HSC compartment and uncover potential molecular mechanisms linking obesity to hematological diseases. Notably our results support the intriguing possibility that obesity, by directly acting on the HSC compartment, contributes to the development of a clonal hematopoiesis and favors the emergence of aberrant HSC clones. Disclosures No relevant conflicts of interest to declare.

scholarly journals A genome-wide search for epigenetically regulated genes in zebra finch using MethylCap-seq and RNA-seq

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Sandra Steyaert ◽  
Jolien Diddens ◽  
Jeroen Galle ◽  
Ellen De Meester ◽  
Sarah De Keulenaer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Zebra Finch ◽  
Model Organism ◽  
Rna Seq ◽  
Exon Arrays ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Search ◽  
Upregulated Genes

Abstract Learning and memory formation are known to require dynamic CpG (de)methylation and gene expression changes. Here, we aimed at establishing a genome-wide DNA methylation map of the zebra finch genome, a model organism in neuroscience, as well as identifying putatively epigenetically regulated genes. RNA- and MethylCap-seq experiments were performed on two zebra finch cell lines in presence or absence of 5-aza-2′-deoxycytidine induced demethylation. First, the MethylCap-seq methodology was validated in zebra finch by comparison with RRBS-generated data. To assess the influence of (variable) methylation on gene expression, RNA-seq experiments were performed as well. Comparison of RNA-seq and MethylCap-seq results showed that at least 357 of the 3,457 AZA-upregulated genes are putatively regulated by methylation in the promoter region, for which a pathway analysis showed remarkable enrichment for neurological networks. A subset of genes was validated using Exon Arrays, quantitative RT-PCR and CpG pyrosequencing on bisulfite-treated samples. To our knowledge, this study provides the first genome-wide DNA methylation map of the zebra finch genome as well as a comprehensive set of genes of which transcription is under putative methylation control.

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