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.

scholarly journals Genome-wide kinetic properties of transcriptional bursting in mouse embryonic stem cells

2020 ◽  
Vol 6 (25) ◽  
pp. eaaz6699 ◽  
Author(s):  
Hiroshi Ochiai ◽  
Tetsutaro Hayashi ◽  
Mana Umeda ◽  
Mika Yoshimura ◽  
Akihito Harada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Mammalian Cells ◽  
Transcription Elongation ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Kinetic Properties ◽  
Mrna Levels ◽  
Transcriptional Bursting

Transcriptional bursting is the stochastic activation and inactivation of promoters, contributing to cell-to-cell heterogeneity in gene expression. However, the mechanism underlying the regulation of transcriptional bursting kinetics (burst size and frequency) in mammalian cells remains elusive. In this study, we performed single-cell RNA sequencing to analyze the intrinsic noise and mRNA levels for elucidating the transcriptional bursting kinetics in mouse embryonic stem cells. Informatics analyses and functional assays revealed that transcriptional bursting kinetics was regulated by a combination of promoter- and gene body–binding proteins, including the polycomb repressive complex 2 and transcription elongation factors. Furthermore, large-scale CRISPR-Cas9–based screening identified that the Akt/MAPK signaling pathway regulated bursting kinetics by modulating transcription elongation efficiency. These results uncovered the key molecular mechanisms underlying transcriptional bursting and cell-to-cell gene expression noise in mammalian cells.

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 A Genome-Wide Analysis of the Effects of Sucrose on Gene Expression in Arabidopsis Seedlings under Anoxia

2005 ◽  
Vol 137 (3) ◽  
pp. 1130-1138 ◽  
Author(s):  
Elena Loreti ◽  
Alessandra Poggi ◽  
Giacomo Novi ◽  
Amedeo Alpi ◽  
Pierdomenico Perata
Keyword(s):  
Gene Expression ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome
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