Microgravity-Induced Alterations in the H3.3B (H3F3B) Gene Expression and the Histone H3 Structure

2020 ◽  
Vol 12 (8) ◽  
pp. 1084-1094
Author(s):  
Azadeh Hekmat ◽  
Mojtaba Sadeghi Manesh ◽  
Zahra Hajebrahimi ◽  
Shadie Hatamie
Keyword(s):  
Gene Expression ◽  
Simulated Microgravity ◽  
Tertiary Structure ◽  
Gene Expression Regulation ◽  
Molten Globule ◽  
Histone H3 ◽  
Fluorescence Emission ◽  
Surface Hydrophobicity ◽  
Expression Level ◽  
Visible Absorption

It has been believed that microgravity directly can modify the structure, function, and morphology of biosystems and numerous researches have been performed to recognize these alterations. Since histone H3 is an essential protein in the field of epigenetics, this research aimed to evaluate the effects of simulated microgravity on the human H3.3B (H3F3B) gene expression and histone H3 structure. The two-dimensional clinostat was applied for simulating microgravity. Analysis of the gene expression by real-time quantitative PCR revealed that simulated microgravity diminished the expression level of H3.3B considerably (P < 0.001). The UV-Visible absorption and extrinsic fluorescence emission results displayed that after 72 h of simulated microgravity the tertiary structure of histone H3 changed and the surface hydrophobicity of the protein incremented remarkably. Nevertheless, circular dichroism (CD) data showed that simulated microgravity did not perturb the secondary structure of histone H3. Collectively, microgravity can strictly affect the gene expression level of H3.3. Furthermore, histone H3 72 h after subjecting to simulated microgravity can exhibit a molten globule structure. The significance of this research lied in the fact that simulating microgravity can be an effective physical force in gene expression regulation and the protein folding process. This finding could help astrobiologists to realize major health risks for astronaut crews and space travelers and reduce these harmful effects. Furthermore, our observations can open fascinating research lines in astrobiology, biophysics, and exobiology.

Intermediate studies on refolding of arginine kinase denatured by guanidine hydrochloride

2005 ◽  
Vol 83 (2) ◽  
pp. 109-114 ◽  
Author(s):  
Hong-Min Tang ◽  
Hong Yu
Keyword(s):  
Fluorescence Intensity ◽  
Tertiary Structure ◽  
Structural Characteristics ◽  
Molten Globule ◽  
Guanidine Hydrochloride ◽  
Arginine Kinase ◽  
Fluorescence Emission ◽  
Tryptophan Fluorescence ◽  
Blue Shift ◽  
Molten Globule State

The refolding course and intermediate of guanidine hydrochloride (GuHCl)-denatured arginine kinase (AK) were studied in terms of enzymatic activity, intrinsic fluorescence, 1-anilino-8-naphthalenesulfonte (ANS) fluorescence, and far-UV circular dichroism (CD). During AK refolding, the fluorescence intensity increased with a significantly blue shift of the emission maximum. The molar ellipticity of CD increased to close to that of native AK, as compared with the fully unfolded AK. In the AK refolding process, 2 refolding intermediates were observed at the concentration ranges of 0.8–1.0 mol/L and 0.3–0.5 mol GuHCl/L. The peak position of the fluorescence emission and the secondary structure of these conformation states remained roughly unchanged. The tryptophan fluorescence intensity increased a little. However, the ANS fluorescence intensity significantly increased, as compared with both the native and the fully unfolded states. The first refolding intermediate at the range of 0.8–1.0 mol GuHCl/L concentration represented a typical "pre-molten globule state structure" with inactivity. The second one, at the range of 0.3–0.5 mol GuHCl/L concentration, shared many structural characteristics of native AK, including its secondary and tertiary structure, and regained its catalytic function, although its activity was lower than that of native AK. The present results suggest that during the refolding of GuHCl-denatured AK there are at least 2 refolding intermediates; as well, the results provide direct evidence for the hierarchical mechanism of protein folding.Key words: arginine kinase, guanidine-denatured, refolding, intermediate, molten globule state.

scholarly journals RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis

2017 ◽  
Vol 214 (6) ◽  
pp. 1843-1855 ◽  
Author(s):  
Yan Xia ◽  
Weiwei Yang ◽  
Ming Fa ◽  
Xinjian Li ◽  
Yugang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Gene Expression Regulation ◽  
Chromatin Modification ◽  
Histone H3 ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Promoter Regions ◽  
Dependent Protein ◽  
Nucleosome Disassembly

Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2–phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription. RNF8-mediated histone H3 polyubiquitylation promotes tumor cell glycolysis and proliferation and brain tumorigenesis. Our findings uncover the role of RNF8-mediated histone H3 polyubiquitylation in the regulation of histone H3 stability and chromatin modification, paving the way to gene expression regulation and tumorigenesis.

scholarly journals Effects of HTR1B 3' region polymorphisms and functional regions on gene expression regulation

2020 ◽  
Author(s):  
xi xia ◽  
Mei Ding ◽  
Jin-feng Xuan ◽  
Jia-xin Xing ◽  
Hao Pang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Inhibitory Effect ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Negative Effects ◽  
Hek 293 ◽  
Functional Regions ◽  
Regulatory Effects ◽  
Post Transcriptional Regulation

Abstract Background The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3' regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3' region of HTR1B. Methods Seven haplotypes, consisting of rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041, and truncated fragments of the HTR1B gene 3' region were transfected into SK-N-SH, HEK-293, and U87 cell lines. The relative fluorescence intensities were detected by a dual luciferase reporter assay system.Results We found that the haplotype, AG_CT_A, enhanced the expression level compared to the main haplotype; AG_CG_A; GG_CG_G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that +2440 ~ +2769 bp and +1953 ~ +2311 bp regions both had negative effects on gene expression.ConclusionsThe 3' region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3' region includes several effector binding sites that induce an inhibitory effect on gene expression.

scholarly journals A comprehensive epigenomic analysis of phenotypically distinguishable, genetically identical female and male Daphnia pulex

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jouni Kvist ◽  
Camila Gonçalves Athanàsio ◽  
Michael E. Pfrender ◽  
James B. Brown ◽  
John K. Colbourne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone H3 ◽  
Daphnia Pulex ◽  
Epigenetic Modifications ◽  
The Other ◽  
Gene Expression Level ◽  
Expression Level ◽  
Male And Female ◽  
Phenotypic Differences

Abstract Background Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. Results In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine 4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine 27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. Conclusions The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.

Gene expression regulation by heat-shock proteins: the cardinal roles of HSF1 and Hsp90

2017 ◽  
Vol 46 (1) ◽  
pp. 51-65 ◽  
Author(s):  
Gisela I. Mazaira ◽  
Cristina Daneri-Becerra ◽  
Nadia R. Zgajnar ◽  
Cecilia M. Lotufo ◽  
Mario D. Galigniana
Keyword(s):  
Gene Expression ◽  
Heat Shock ◽  
Protein Function ◽  
Histone Deacetylases ◽  
Tertiary Structure ◽  
Gene Expression Regulation ◽  
Heat Shock Protein 90 ◽  
Heat Shock Factor 1 ◽  
Client Proteins ◽  
Shock Proteins

The ability to permit gene expression is managed by a set of relatively well known regulatory mechanisms. Nonetheless, this property can also be acquired during a life span as a consequence of environmental stimuli. Interestingly, some acquired information can be passed to the next generation of individuals without modifying gene information, but instead by the manner in which cells read and process such information. Molecular chaperones are classically related to the proper preservation of protein folding and anti-aggregation properties, but one of them, heat-shock protein 90 (Hsp90), is a refined sensor of protein function facilitating the biological activity of properly folded client proteins that already have a preserved tertiary structure. Interestingly, Hsp90 can also function as a critical switch able to regulate biological responses due to its association with key client proteins such as histone deacetylases or DNA methylases. Thus, a growing amount of evidence has connected the action of Hsp90 to post-translational modifications of soluble nuclear factors, DNA, and histones, which epigenetically affect gene expression upon the onset of an unfriendly environment. This response is commanded by the activation of the transcription factor heat-shock factor 1 (HSF1). Even though numerous stresses of diverse nature are known to trigger the stress response by activation of HSF1, it is still unknown whether there are different types of molecular sensors for each type of stimulus. In the present review, we will discuss various aspects of the regulatory action of HSF1 and Hsp90 on transcriptional regulation, and how this regulation may affect genetic assimilation mechanisms and the health of individuals.

scholarly journals AN OVERVIEW ON MECHANISM OF GENE EXPRESSION REGULATION

2021 ◽  
Vol 52 (2) ◽  
pp. 454-460
Author(s):  
M. M. Elsahookie ◽  
S. H. Cheyed ◽  
A. A. Dawood
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Gene Expression Regulation ◽  
Molecular Level ◽  
Histone H3 ◽  
Three Dimensions ◽  
Transition Rates ◽  
Biotic And Abiotic Stresses ◽  
Protein Coding ◽  
Living Organisms

Transcription factors, enhancers, promoters, and translation of genetic code is still in a wide argument of different views in many living organisms for their poorly characterized at the molecular level. It was shown that the coexistence of high mono – methylation levels of lysine 4 of histone H3 is considered a signature of enhancers. Gene expression could be altered by epigenetic and some biotic and abiotic stresses. Some sugars, hormones or amino acids could also alter gene expression. However, some investigators have shown that increased methylation  at promoters was associated with down – regulated protein – coding gene expression . In genomic DNA methylation levels, it was found 24 nt small RNAs only were correlated with methylation. Other investigators have set framework for modelling gene regulation, three dimensions were set to draw the graph framework; DNA microstates (vertices), the transitions between microstates, (edges) and the transition rates (edge labels). They believed that their graph will provide a broader foundation for understanding how genes regulate their expressions. More recently, a team of Australian investigators in Medical Res. have shown a new i-motifs; a four–stranded DNA knot in living human cells. These i- motifs were believed to be responsible in helping genes to switch on or off. Future investigations in gene expression will probably be shown in different models than we have learned. 

scholarly journals Adult-specific trimethylation of histone H3 lysine 4 is prone to dynamic changes with aging in C. elegans somatic cells

2017 ◽  
Author(s):  
Mintie Pu ◽  
Minghui Wang ◽  
Wenke Wang ◽  
Satheeja Santhi Velayudhan ◽  
Siu Sylvia Lee
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Developmental Stages ◽  
Gene Expression Regulation ◽  
Histone H3 ◽  
Expression Regulation ◽  
Rna Expression ◽  
Dynamic Changes ◽  
C Elegans ◽  
Expression Of Genes

AbstractTri-methylation on histone H3 lysine 4 (H3K4me3) is associated with active gene expression but its regulatory role in transcriptional activation is unclear. Here we used Caenorhabditis elegans to investigate the connection between H3K4me3 and gene expression regulation during aging. We uncovered around 30% of H3K4me3 enriched regions to show significant and reproducible changes with age. We further showed that these age-dynamic H3K4me3 regions largely mark gene-bodies and are acquired during adult stages. We found that these adult-specific age-dynamic H3K4me3 regions are correlated with gene expression changes with age. In contrast, H3K4me3 marking established during developmental stages remained largely stable with age, even when the H3K4me3 associated genes exhibited RNA expression changes during aging. Moreover, we found that global reduction of H3K4me3 levels results in significantly decreased RNA expression of genes that acquire H3K4me3 marking in their gene-bodies during adult stage, suggesting that altered H3K4me3 levels with age could result in age-dependent gene expression changes. Interestingly, the genes with dynamic changes in H3K4me3 and RNA levels with age are enriched for those involved in fatty acid metabolism, oxidation-reduction, and stress response. Therefore, our findings revealed divergent roles of H3K4me3 in gene expression regulation during aging, with important implications on physiological relevance.

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