scholarly journals Stochastic gene expression drives mesophyll protoplast regeneration

2021 ◽  
Vol 7 (33) ◽  
pp. eabg8466
Author(s):  
Mengxue Xu ◽  
Qingwei Du ◽  
Caihuan Tian ◽  
Ying Wang ◽  
Yuling Jiao
Keyword(s):  
Gene Expression ◽  
Low Frequency ◽  
Mesophyll Protoplast ◽  
Underlying Mechanism ◽  
Protoplast Isolation ◽  
Chromatin Accessibility ◽  
Cellular Level ◽  
Protoplast Regeneration ◽  
Expression Variability ◽  
Enhanced Expression

Cell pluripotency is fundamental to biology. It has long been known that differentiated somatic plant cells may reacquire pluripotency, but the underlying mechanism remains elusive. In many plant species, a single isolated mesophyll protoplast may regenerate into an entire plant, which is widely used in gene transformation. Here, we identified two transcription factors whose ectopic activation promotes protoplast regeneration. Furthermore, we found that their expression was induced by protoplast isolation but at a very low frequency. Using live imaging and single-cell transcriptomics, we show that isolating protoplasts induces enhanced expression variation at the genome level. Isolating protoplasts also leads to genome-wide increases in chromatin accessibility, which promotes stochastic activation of gene expression and enhances protoplast regeneration. We propose that transcriptome chaos with increased expression variability among cells creates a cellular-level evolutionary driver selecting for regenerating cells.

scholarly journals Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells

2019 ◽  
Author(s):  
Koos Rooijers ◽  
Corina M. Markodimitraki ◽  
Franka J. Rang ◽  
Sandra S. de Vries ◽  
Alex Chialastri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Single Cells ◽  
Critical Role ◽  
Nuclear Lamina ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Expression Variability ◽  
The Impact

AbstractThe epigenome plays a critical role in regulating gene expression in mammalian cells. However, understanding how cell-to-cell heterogeneity in the epigenome influences gene expression variability remains a major challenge. Here we report a novel method for simultaneous single-cell quantification of protein-DNA contacts with DamID and transcriptomics (scDamID&T). This method enables quantifying the impact of protein-DNA contacts on gene expression from the same cell. By profiling lamina-associated domains (LADs) in human cells, we reveal different dependencies between genome-nuclear lamina (NL) association and gene expression in single cells. In addition, we introduce the E. coli methyltransferase, Dam, as an in vivo marker of chromatin accessibility in single cells and show that scDamID&T can be utilized as a general technology to identify cell types in silico while simultaneously determining the underlying gene-regulatory landscape. With this strategy the effect of chromatin states, transcription factor binding, and genome organization on the acquisition of cell-type specific transcriptional programs can be quantified.

scholarly journals Epigenetic mechanisms of partial dosage compensation in an avian, female heterogametic system

2021 ◽  
Author(s):  
Ana Catalan ◽  
Jochen Wolf ◽  
Justin Merondun ◽  
Ulrich Knief
Keyword(s):  
Gene Expression ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Gene Dosage ◽  
Common Garden ◽  
Underlying Mechanism ◽  
Chromatin Accessibility ◽  
Z Chromosome ◽  
Open Chromatin ◽  
Epigenetic Mechanisms

The evolution of genetic sex determination is often accompanied by degradation of one of the proto sex chromosomes. Male heterogametic systems have evolved convergent, epigenetic mechanisms restoring the resulting imbalance in gene dosage between diploid autosomes (AA) and the hemizygous sex chromosome (X). Female heterogametic systems (AAf ZWf, AAm ZZm) tend to only show partial dosage compensation (0.5 < Zf:AAf < 1) and dosage balance (0.5<Zf:ZZm<1). The underlying mechanism remains largely elusive. Here, we quantified gene expression for a total of 15 male and female Eurasian crows (Corvus (corone) spp.) raised under common garden conditions. In addition, we characterized aspects of the regulatory landscape quantifying genome-wide ATAC-seq and 5mC methylation profiles. Partial dosage compensation was explained by female upregulation of Z-linked genes accompanied by increased chromatin accessibility on the female Z chromosome. 5mC methylation was strongly reduced in open chromatin-regions and GC islands and showed chromosome-, but no sex-specific variation. With the exception of the pseudo-autosomal region (PAR), female upregulation of gene expression was evenly spread across the Z chromosome without evidence for regional epigenetic regulation, as has for example been suggested for the male hypermethylated region (MHM) in chicken. Our results support the hypothesis that partial dosage compensation in female heterogametic systems is subject to chromosome-wide, epigenetic control mediated by differential chromatin accessibility between the sexes.

A Method of Pathway Enrichment Analysis Based Gene Expression Variability

2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Expression Variability ◽  
Pathway Enrichment

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

scholarly journals Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karolina Stępniak ◽  
Magdalena A. Machnicka ◽  
Jakub Mieczkowski ◽  
Anna Macioszek ◽  
Bartosz Wojtaś ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Molecular Mechanisms ◽  
Genome Mapping ◽  
Malignant Gliomas ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Multiple Tumor ◽  
Genes Encoding ◽  
Methylation Patterns

AbstractChromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.

HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway

2021 ◽  
Author(s):  
Yong Fu ◽  
Gailing Ma ◽  
Yuqian Zhang ◽  
Wenli Wang ◽  
Tongguo Shi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Camp Response Element Binding ◽  
Cellular Level ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Colitis ◽  
Anti Inflammatory

Abstract Background Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that plays a pivotal role in maintaining mucosal immune homeostasis. As a novel synthetic inhibitor of salt-inducible kinases (SIKs), HG-9-91-01 can effectively enhance IL-10 secretion at the cellular level, but its in vivo immunoregulatory effects remain unclear. In this study, we investigated the effects and underlying mechanism of HG-9-91-01 in murine colitis models. Methods The anti-inflammatory effects of HG-9-91-01 were evaluated on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium–induced colitis mice, and IL-10 knockout chronic colitis mice. The in vivo effector cell of HG-9-91-01 was identified by fluorescence-activated cell sorting and quantitative real-time polymerase chain reaction. The underlying mechanism of HG-9-91-01 was investigated via overexpressing SIKs in ANA-1 macrophages and TNBS colitis mice. Results Treatment with HG-9-91-01 showed favorable anticolitis effects in both TNBS- and DSS-treated mice through significantly promoting IL-10 expression in colonic macrophages but failed to protect against IL-10 KO murine colitis. Further study indicated that HG-9-91-01 markedly enhanced the nuclear level of cAMP response element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3), whereas treatment with lentiviruses encoding SIK protein markedly decreased the nuclear CRTC3 level in HG-9-91-01–treated ANA-1 macrophages. In addition, intracolonic administration with lentiviruses encoding SIK protein significantly decreased the nuclear CRTC3 level in the lamina propria mononuclear cells and ended the anti-inflammatory activities of HG-9-91-01. Conclusions We found that HG-9-91-01 promoted the IL-10 expression of colonic macrophages and exhibited its anticolitis activity through the SIK/CRTC3 axis, and thus it may represent a promising strategy for inflammatory bowel disease therapy.

scholarly journals Leveraging epigenetics to enhance the efficacy of immunotherapy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jonathan D. Licht ◽  
Richard L. Bennett
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Antigen Presentation ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Epigenetic Modifications ◽  
Main Body ◽  
Epigenetic Mechanisms

Abstract Background Epigenetic mechanisms regulate chromatin accessibility patterns that govern interaction of transcription machinery with genes and their cis-regulatory elements. Mutations that affect epigenetic mechanisms are common in cancer. Because epigenetic modifications are reversible many anticancer strategies targeting these mechanisms are currently under development and in clinical trials. Main body Here we review evidence suggesting that epigenetic therapeutics can deactivate immunosuppressive gene expression or reprogram tumor cells to activate antigen presentation mechanisms. In addition, the dysregulation of epigenetic mechanisms commonly observed in cancer may alter the immunogenicity of tumor cells and effectiveness of immunotherapies. Conclusions Therapeutics targeting epigenetic mechanisms may be helpful to counter immune evasion and improve the effectiveness of immunotherapies.

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

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

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