scholarly journals Confounding factors from inducible systems for spatiotemporal gene expression regulation

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Rob C.I. Wüst ◽  
Riekelt H. Houtkooper ◽  
Johan Auwerx
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Whole Body ◽  
Phenotypic Traits ◽  
Gene Variants ◽  
Metabolic Function ◽  
Confounding Factors ◽  
Inducible Systems ◽  
And Function ◽  
Target Effects

Spatiotemporally regulated targeted gene manipulation is a common way to study the effect of gene variants on phenotypic traits, but the Cre/loxP and Tet-On/Tet-Off systems can affect whole-organism physiology and function due to off-target effects. We highlight some of these adverse effects, including whole-body endocrinology and disturbances in the gut microbiome and in mitochondrial and metabolic function.

scholarly journals The essential activities of the bacterial sigma factor

2017 ◽  
Vol 63 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Maria C. Davis ◽  
Christopher A. Kesthely ◽  
Emily A. Franklin ◽  
Shawn R. MacLellan
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Rna Synthesis ◽  
Gene Expression Regulation ◽  
Structure And Function ◽  
Structural Studies ◽  
General Transcription Factors ◽  
Transcription Process ◽  
Promoter Dna ◽  
And Function

Transcription is the first and most heavily regulated step in gene expression. Sigma (σ) factors are general transcription factors that reversibly bind RNA polymerase (RNAP) and mediate transcription of all genes in bacteria. σ Factors play 3 major roles in the RNA synthesis initiation process: they (i) target RNAP holoenzyme to specific promoters, (ii) melt a region of double-stranded promoter DNA and stabilize it as a single-stranded open complex, and (iii) interact with other DNA-binding transcription factors to contribute complexity to gene expression regulation schemes. Recent structural studies have demonstrated that when σ factors bind promoter DNA, they capture 1 or more nucleotides that are flipped out of the helical DNA stack and this stabilizes the promoter open-complex intermediate that is required for the initiation of RNA synthesis. This review describes the structure and function of the σ70 family of σ proteins and the essential roles they play in the transcription process.

scholarly journals Effect of β-adrenergic receptor agents on cardiac structure and function and whole-body gene expression in Daphnia magna

2018 ◽  
Vol 241 ◽  
pp. 869-878 ◽  
Author(s):  
Tae-Yong Jeong ◽  
Jana Asselman ◽  
Karel A.C. De Schamphelaere ◽  
Filip Van Nieuwerburgh ◽  
Dieter Deforce ◽  
...  
Keyword(s):  
Gene Expression ◽  
Daphnia Magna ◽  
Adrenergic Receptor ◽  
Structure And Function ◽  
Whole Body ◽  
Cardiac Structure ◽  
Cardiac Structure And Function ◽  
And Function

Bombesin-like peptide receptor gene expression, regulation, and function in fetal murine lung

2004 ◽  
Vol 286 (1) ◽  
pp. L165-L173 ◽  
Author(s):  
Lin Shan ◽  
Rodica L. Emanuel ◽  
Denise Dewald ◽  
John S. Torday ◽  
Nithiananthan Asokanathan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Development ◽  
Gene Expression Regulation ◽  
Receptor Gene ◽  
Fetal Lung ◽  
Mouse Lung ◽  
Receptor Subtype ◽  
Fetal Lung Development ◽  
And Function ◽  
Receptor Gene Expression

Bombesin-peptide (BLP) immunoreactivity occurs at high levels in fetal lung. Previous studies showed that bombesin promotes fetal lung development. To test the hypothesis that such effects are mediated by known mammalian bombesin receptors [gastrin-releasing peptide (GRP)/bombesin-preferring receptor (GRPR), neuromedin B (NMB) receptor (NMBR), and the orphan bombesin receptor subtype-3 (BRS-3)], we analyzed the ontogeny of GRPR, NMBR, and BRS-3 gene expression in mouse lung. We examined the regulation of these three genes by dexamethasone and bombesin, which modulate lung development. Using incorporation of [3H]thymidine and [3H]choline, we then assessed whether GRP, NMB, and Leu8-phyllolitorin modulate lung growth and maturation in fetal lung explants. GRPR gene expression was detected predominantly in utero, whereas NMBR and BRS-3 genes were expressed from embryonic days 13–16 and on multiple postnatal days. All three mRNAs are present in airway epithelium and mesenchymal cells but occur in different relative patterns. These genes were regulated differently. Dexamethasone and bombesin increased GRPR mRNA, bombesin downregulated NMBR, and neither agent affected BRS-3. GRP increased incorporation of [3H]thymidine and [3H]choline in explants, whereas NMB induced cell proliferation and Leu8-phyllolitorin yielded variable results. Cumulative data suggest the involvement of multiple BLP receptors, including novel molecules, and argue against simple functional redundancy within this gene family during lung development.

scholarly journals Role of Tet2 in Regulating Adaptive and Innate Immunity

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiaqi Li ◽  
Lifang Li ◽  
Xiaoxiao Sun ◽  
Tuo Deng ◽  
Gan Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Targets ◽  
Gene Expression Regulation ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Cellular Factors ◽  
Tet Enzymes ◽  
And Function ◽  
Opposing Effects ◽  
Tet Protein

Accumulated evidence indicates that epigenetic modifications play central roles in gene expression regulation and participate in developing many autoimmune and autoinflammatory diseases. Mechanistically, epigenetic modifications act as a bridge between environmental and cellular factors and susceptibility genes. DNA methylation is a critical epigenetic modification that is regulated by ten-eleven translocation (TET) enzymes. Accumulating evidence has revealed that TET family proteins function as gene regulators and antitumor drug targets mainly because of their ability to oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Recently, the effect of Tet2, an essential TET protein, on the development of autoimmune diseases has been explored. In this review, we summarize the current understanding of Tet2 in immune response regulation, clarify the mechanisms of Tet2 in B and T cell differentiation and function, and discuss the opposing effects of Tet2 on inflammatory gene expression in the immune system to provide new potential therapeutic targets for related diseases.

scholarly journals Trichomonas vaginalisCysteine Proteinases: Iron Response in Gene Expression and Proteolytic Activity

2015 ◽  
Vol 2015 ◽  
pp. 1-24 ◽  
Author(s):  
Rossana Arroyo ◽  
Rosa Elena Cárdenas-Guerra ◽  
Elisa Elvira Figueroa-Angulo ◽  
Jonathan Puente-Rivera ◽  
Olga Zamudio-Prieto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Proteolytic Activity ◽  
Trichomonas Vaginalis ◽  
Genomic Organization ◽  
Gene Expression Regulation ◽  
Cathepsin L ◽  
Protein Levels ◽  
Large Gene ◽  
And Function

We focus on the iron response ofTrichomonas vaginalisto gene family products such as the cysteine proteinases (CPs) involved in virulence properties. In particular, we examined the effect of iron on the gene expression regulation and function of cathepsin L-like and asparaginyl endopeptidase-like CPs as virulence factors. We addressed some important aspects about CPs genomic organization and we offer possible explanations to the fact that only few members of this large gene family are expressed at the RNA and protein levels and the way to control their proteolytic activity. We also summarized all known iron regulations of CPs at transcriptional, posttranscriptional, and posttranslational levels along with new insights into the possible epigenetic and miRNA processes.

scholarly journals Tudor staphylococcal nuclease acts as a docking platform for stress granule components in Arabidopsis thaliana

2020 ◽  
Author(s):  
Emilio Gutierrez-Beltran ◽  
Pernilla H. Elander ◽  
Kerstin Dalman ◽  
Jose Luis Crespo ◽  
Panagiotis N. Moschou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Cell Biology ◽  
Gene Expression Regulation ◽  
De Novo ◽  
Staphylococcal Nuclease ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Stress Dependent ◽  
And Function

SUMMARYAdaptation to stress depends on the modulation of gene expression. Regulation of mRNA stability and degradation in stress granules (SGs), - cytoplasmic membraneless organelles composed of messenger ribonucleoprotein (mRNP) complexes, - plays an important role in fine-tuning of gene expression. In addition, SG formation can modulate stress signaling pathways by protein sequestration. Molecular composition, structure, and function of SGs in plants remain obscure. Recently, we established Tudor Staphylococcal Nuclease (TSN or Tudor-SN; also known as SND1) as integral component of SGs in Arabidopsis thaliana. Here, we combined purification of TSN interactome with cell biology, reverse genetics and bioinformatics to study composition and function of SGs in plants. We found that under both normal (in the absence of stress) and stress conditions TSN interactome is enriched in the homologues of known mammalian and yeast SG proteins, in addition to novel or plant-specific SG components. We estimate that upon stress perception, approximately half of TSN interactors are recruited to SGs de novo, in a stress-dependent manner, while another half represent a dense protein-protein interaction network pre-formed before onset of stress. Almost all TSN-interacting proteins are moderately or highly disordered and approximately 20% of them are predisposed for liquid-liquid phase separation (LLPS). This suggests that plant SGs, similarly to mammalian and yeast counterparts, are multicomponent viscous liquid droplets. Finally, we have discovered that evolutionary conserved SNF1-related protein kinase 1 (SnRK1) interacts with TSN in heat-induced SGs and that SnRK1 activation critically depends on the presence of TSN and formation of SGs. Altogether, our results establish TSN as a docking platform for SG-associated proteins and important stress signal mediator in plants.

scholarly journals Integrated Study of Transcriptome-wide m6A Methylome Reveals Novel Insights Into the Character and Function of m6A Methylation During Yak Adipocyte Differentiation

2021 ◽  
Vol 9 ◽  
Author(s):  
Yongfeng Zhang ◽  
Chunnian Liang ◽  
Xiaoyun Wu ◽  
Jie Pei ◽  
Xian Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Gene Expression Regulation ◽  
Positive Association ◽  
Cold Season ◽  
Vital Role ◽  
Functional Enrichment ◽  
Differentially Methylated Genes ◽  
And Function

Yak (Bos grunniens) is considered an iconic symbol of Tibet and high altitude, but they suffer from malnutrition during the cold season that challenges the metabolism of energy. Adipocytes perform a crucial role in maintaining the energy balance, and adipocyte differentiation is a complex process involving multiple changes in the expression of genes. N6-methyladenosine (m6A) plays a dynamic role in post-transcription gene expression regulation as the most widespread mRNA modification of the higher eukaryotes. However, currently there is no research existing on the m6A transcriptome-wide map of bovine animals and their potential biological functions in adipocyte differentiation. Therefore, we performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to determine the distinctions in m6A methylation and gene expression during yak adipocyte differentiation. In yak adipocyte and preadipocyte the content of m6A and m6A-associated enzymes was substantially different. In the two groups, a total of 14,710 m6A peaks and 13,388 m6A peaks were identified. For the most part, m6A peaks were enriched in stop codons, 3′-untranslated regions, and coding regions with consensus motifs of GGACU. The functional enrichment exploration displayed that differentially methylated genes participated in some of the pathways associated with adipogenic metabolism, and several candidate genes (KLF9, FOXO1, ZNF395, and UHRF1) were involved in these pathways. In addition to that, there was a positive association between m6A abundance and levels of gene expression, which displayed that m6A may play a vital role in modulating gene expression during yak adipocyte differentiation. Further, in the adipocyte group, several methylation gene protein expression levels were significantly higher than in preadipocytes. In short, it can be concluded that the current study provides a comprehensive explanation of the m6A features in the yak transcriptome, offering in-depth insights into m6A topology and associated molecular mechanisms underlying bovine adipocyte differentiation, which might be helpful for further understanding its mechanisms.

scholarly journals Out of sight, out of mind? Germ cells and the potential impacts of epigenomic drugs

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1967 ◽  
Author(s):  
Ellen G. Jarred ◽  
Heidi Bildsoe ◽  
Patrick S. Western
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Modifications ◽  
Germ Cells ◽  
Epigenetic Modifications ◽  
Reproductive Age ◽  
Specific Gene ◽  
And Function ◽  
Substantial Interest ◽  
Target Effects

Epigenetic modifications, including DNA methylation and histone modifications, determine the way DNA is packaged within the nucleus and regulate cell-specific gene expression. The heritability of these modifications provides a memory of cell identity and function. Common dysregulation of epigenetic modifications in cancer has driven substantial interest in the development of epigenetic modifying drugs. Although these drugs have the potential to be highly beneficial for patients, they act systemically and may have “off-target” effects in other cells such as the patients’ sperm or eggs. This review discusses the potential for epigenomic drugs to impact on the germline epigenome and subsequent offspring and aims to foster further examination into the possible effects of these drugs on gametes. Ultimately, the information gained by further research may improve the clinical guidelines for the use of such drugs in patients of reproductive age.

Sign in / Sign up

Export Citation Format

Share Document