Chromatin Signature and Transcription Factor Binding Provide a Predictive Basis for Understanding Plant Gene Expression

2019 ◽  
Vol 60 (7) ◽  
pp. 1471-1486 ◽  
Author(s):  
Zefeng Wu ◽  
Jing Tang ◽  
Junjie Zhuo ◽  
Yuhan Tian ◽  
Feiyang Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Histone Modifications ◽  
Gene Expression Level ◽  
Expression Level ◽  
Good Prediction ◽  
Chromatin Modifications ◽  
Chromatin Signature ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Chromatin accessibility and post-transcriptional histone modifications play important roles in gene expression regulation. However, little is known about the joint effect of multiple chromatin modifications on the gene expression level in plants, despite that the regulatory roles of individual histone marks such as H3K4me3 in gene expression have been well-documented. By using machine-learning methods, we systematically performed gene expression level prediction based on multiple chromatin modifications data in Arabidopsis and rice. We found that as few as four histone modifications were sufficient to yield good prediction performance, and H3K4me3 and H3K36me3 being the top two predictors with known functions related to transcriptional initiation and elongation, respectively. We demonstrated that the predictive powers differed between protein-coding and non-coding genes as well as between CpG-enriched and CpG-depleted genes. We also showed that the predictive model trained in one tissue or species could be applied to another tissue or species, suggesting shared underlying mechanisms. More interestingly, the gene expression levels of conserved orthologs are easier to predict than the species-specific genes. In addition, chromatin state of distal enhancers was moderately correlated to gene expression but was dispensable if given the chromatin features of the proximal regions of genes. We further extended the analysis to transcription factor (TF) binding data. Strikingly, the combinatorial effects of only a few TFs were roughly fit to gene expression levels in Arabidopsis. Overall, by using quantitative modeling, we provide a comprehensive and unbiased perspective on the epigenetic and TF-mediated regulation of gene expression in plants.

scholarly journals Methylation QTLs Are Associated with Coordinated Changes in Transcription Factor Binding, Histone Modifications, and Gene Expression Levels

PLoS Genetics ◽  
2014 ◽  
Vol 10 (9) ◽  
pp. e1004663 ◽  
Author(s):  
Nicholas E. Banovich ◽  
Xun Lan ◽  
Graham McVicker ◽  
Bryce van de Geijn ◽  
Jacob F. Degner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Histone Modifications ◽  
Transcription Factor Binding ◽  
Expression Levels ◽  
Factor Binding ◽  
Gene Expression Levels

ATF3 and EGR2 gene expression levels in sdLDL-treated macrophages of patients with coronary artery stenosis

2018 ◽  
Vol 42 (1-2) ◽  
pp. 23-29
Author(s):  
Sayed R. Hosseini-Fard ◽  
Mohsen Khosravi ◽  
Amaneh Yarnazari ◽  
Parisa Hassanpour ◽  
Abdollah Amirfarhangi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery ◽  
Cholesterol Metabolism ◽  
Quantitative Polymerase Chain Reaction ◽  
Fold Change ◽  
Expression Level ◽  
Control Group ◽  
Expression Levels ◽  
Vessel Disease ◽  
Gene Expression Levels

AbstractBackground:The metabolism of cholesteryl esters (CEs) is under the control of a gene network in macrophages. Several genes such asATF3andEGR2are related to cholesterol metabolism.Methods:In this study, theATF3andEGR2gene expression levels were evaluated in differentiated macrophages of subjects undergoing coronary artery angiography [controls (<5% stenosis), patients (>70% stenosis)] after treatment with small dense low density lipoprotein (sdLDL) particles. Monocytes were isolated using a RosetteSep Kit and were differentiated into macrophages using the M-CSF factor. A modified heparin-MgSO4-PEG method was used for the sdLDL preparation. TheATF3andEGR2gene expression levels were measured by the real-time quantitative polymerase chain reaction (RT-qPCR) technique.Results:In contrast with the control group (p=0.4), theATF3expression level reduced significantly in the differentiated macrophages from all patients [single vessel disease (SVD), fold change 17 times, p=0.02; two vessel disease (2VD), fold change 1.5 times, p=0.05; three vessel disease (3VD), fold change 3.5 times, p=0.04]. Also, theEGR2expression level reduced significantly in all groups (p<0.02). The gene fold changes had no significant differences between the patients (p>0.8).Conclusions:We propose that the failure ofATF3gene expression improves the CE synthesis after sdLDL influx. Furthermore, the reducedEGR2gene expression level in the sdLDL-treated groups may be a negative factor in cholesterol homeostasis.

scholarly journals Lipid Productivity and Biosynthesis Genes Response of Indigenous Chlorella sp. T4 Strain under Different Nitrogen and Phosphorus Load

2021 ◽  
Author(s):  
S’fiso Thuthukani Gumbi ◽  
Ajit Kumar ◽  
Ademola Olufolahan Olaniran
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Physiological Response ◽  
Biomass Yield ◽  
Biodiesel Production ◽  
Gene Expression Level ◽  
Expression Level ◽  
Nitrogen And Phosphorus ◽  
Expression Levels ◽  
Lipid Yield

Abstract Microalgae can synthesize and accumulate high neutral lipids upon exposure to abiotic stress such as nutrient starvation or limitation. In this study, indigenous microalgae Chlorella sp. T4 was cultivated in nitrogen and phosphorus under both limiting and replete conditions. Growth, lipid yield, fatty acid profiles and biosynthetic gene expression levels were determined to ascertain cell’s response under these conditions. An impaired cell growth was observed under nitrogen limiting condition, evident by the lowest biomass yield (0.58±0.03 g L−1) as revealed by low quantum efficiency of photosystem II (Fv/Fm) value and chlorophyll a content. An increase in lipid content yield was observed under nitrogen and phosphorus limiting conditions as compared to the control. Nutrient limiting conditions produced fatty acid methyl ester that is suitable for biodiesel production compared to the control (BG-11). Gene expression analysis using real time q-PCR for photosynthesis (rbcL) and lipid biosynthesis (accD, KAS-1, ω-6 FAD, ω-3 FAD) genes revealed different expression levels under both limiting and replete conditions. Under nutrient limiting conditions, increase in the expression of accD, KAS-1, ω-6 FAD and ω-3 FAD genes was observed, whereas a decrease in rbcL gene expression level was noted. A significant correlation could be drawn between the expression levels of the biosynthetic genes and growth rate, biomass yield, physiological response, lipid yield and fatty acid composition. These results provide an insight into the physiological response and gene expression level under different nutrient levels, which could be harnessed for future genetic engineering of Chlorella sp. T4 for improved lipid production.

scholarly journals In vivo measurements reveal a single 5’ intron is sufficient to increase protein expression level in C. elegans

2018 ◽  
Author(s):  
Matthew M. Crane ◽  
Bryan Sands ◽  
Christian Battaglia ◽  
Brock Johnson ◽  
Soo Yun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Expression Level ◽  
Protein Activity ◽  
Coding Sequence ◽  
Expression Levels ◽  
C Elegans ◽  
Hsp 90 ◽  
Gene Expression Levels

AbstractIntrons can increase gene expression levels using a variety of mechanisms collectively referred to as Intron Mediated Enhancement (IME). To date, the magnitude of IME has been quantified in human cell culture and plant models by comparing intronless reporter gene expression levels to those of intron-bearing reporter genes in vitro (mRNA, Western Blots, protein activity), using genome editing technologies that lacked full control of locus and copy number. Here, for the first time, we quantified IME in vivo, in terms of protein expression levels, using fluorescent reporter proteins expressed from a single, defined locus in Caenorhabditis elegans. To quantify the magnitude of IME, we developed a microfluidic chip-based workflow to mount and image individual animals, including software for operation and image processing. We used this workflow to systematically test the effects of position, number and sequence of introns on two different proteins, mCherry and mEGFP, driven by two different promoters, vit-2 and hsp-90. We found the three canonical synthetic introns commonly used in C. elegans transgenes increased mCherry protein concentration by approximately 50%. The naturally-occurring introns found in hsp-90 also increased mCherry expression level by about 50%. Furthermore, and consistent with prior results examining mRNA levels, protein activity or phenotypic rescue, we found that a single, natural or synthetic, 5’ intron was sufficient for the full IME effect while a 3’ intron was not. IME was also affected by protein coding sequence (50% for mCherry and 80% for mEGFP) but not strongly affected by promoter 46% for hsp-90 and 54% for the stronger vit-2. Our results show that IME of protein expression in C. elegans is affected by intron position and contextual coding sequence surrounding the introns, but not greatly by promoter strength. Our combined controlled transgenesis and microfluidic screening approach should facilitate screens for factors affecting IME and other intron-dependent processes.

scholarly journals Independent regulation of gene expression level and noise by histone modifications

2017 ◽  
Vol 13 (6) ◽  
pp. e1005585 ◽  
Author(s):  
Shaohuan Wu ◽  
Ke Li ◽  
Yingshu Li ◽  
Tong Zhao ◽  
Ting Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Regulation Of Gene Expression ◽  
Gene Expression Level ◽  
Expression Level

scholarly journals Aromatase CYP19A1, progesterone receptor PGR and estrogen receptor ESR1 gene expression in biopsy specimens of endometrioid heterotopia and endometrial tissue by reverse transcription PCR

2019 ◽  
Vol 68 (2) ◽  
pp. 79-86
Author(s):  
Natalia Yu. Shved ◽  
Olga V. Malysheva ◽  
Natalia S. Osinovskaya ◽  
Arseniy S. Molotkov ◽  
Anna A. Tsypurdeyeva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Reverse Transcription ◽  
Comparison Group ◽  
Expression Level ◽  
Tissue Samples ◽  
Expression Levels ◽  
Esr1 Gene ◽  
Gene Expression Levels

Hypothesis/aims of study. Endometriosis is one of the most pressing problems of gynecology. Clarifying the expression of the estrogen receptor (ESR1) and the progesterone receptor (PGR) genes and polymorphisms in the aromatase (CYP19A1) gene in endometriosis will expand the understanding of the pathogenesis of the disease and the causes of resistance to its therapy. The objective of this study was to conduct a comparative analysis of mRNA expression of PGR, ESR1 and CYP19A1 genes in paired samples of the eutopic endometrium and peritoneal endometrioid lesions in order to search for predictive markers of response to hormonal therapy. In the future, this may allow personalizing the selection of hormonal preparations for the treatment of endometriosis. Study design, materials and methods. Reverse transcription real-time PCR made it possible to evaluate CYP19A1, PGR and ESR1 gene expression levels in studied tissue samples from 22 patients with endometriosis and 9 women in the comparison group. Results. Quantitative analysis revealed a high heterogeneity in the expression level of the studied genes, in both the endometrium and endometrioid lesions from patients with endometriosis. In the endometrium of patients in the comparison group, the heterogeneity of the expression level was observed only for the ESR1 gene. Conclusion. Our findings suggest a high variability in CYP19A1, ESR1 and PGR gene expression levels in the endometrium and peritoneal foci in patients with endometriosis. This information indicates the need for an individual approach to prescribing targeted therapy, since it is obvious that the effect of treatment will depend primarily on the availability of a therapeutic target in a particular patient. The absence of a typical expression pattern for each of the genes in patients with endometriosis indicates the heterogeneity of the disease and the need to develop a molecular classification of this common pathology.

scholarly journals Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels

2014 ◽  
Author(s):  
Nicholas E. Banovich ◽  
Xun Lan ◽  
Graham McVicker ◽  
Bryce van de Geijn ◽  
Jacob F. Degner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Genetic Variation ◽  
Histone Modifications ◽  
Transcription Factor Binding ◽  
Dnase I ◽  
Expression Levels ◽  
Factor Binding ◽  
Quantitative Changes

AbstractDNA methylation is an important epigenetic regulator of gene expression. Recent studies have revealed widespread associations between genetic variation and methylation levels. However, the mechanistic links between genetic variation and methylation remain unclear. To begin addressing this gap, we collected methylation data at ∼300,000 loci in lymphoblastoid cell lines (LCLs) from 64 HapMap Yoruba individuals, and genome-wide bisulfite sequence data in ten of these individuals. We identified (at an FDR of 10%) 13,915 cis methylation QTLs (meQTLs)—i.e., CpG sites in which changes in DNA methylation are associated with genetic variation at proximal loci. We found that meQTLs are frequently associated with changes in methylation at multiple CpGs across regions of up to 3 kb. Interestingly, meQTLs are also frequently associated with variation in other properties of gene regulation, including histone modifications, DNase I accessibility, chromatin accessibility, and expression levels of nearby genes. These observations suggest that genetic variants may lead to coordinated molecular changes in all of these regulatory phenotypes. One plausible driver of coordinated changes in different regulatory mechanisms is variation in transcription factor (TF) binding. Indeed, we found that SNPs that change predicted TF binding affinities are significantly enriched for associations with DNA methylation at nearby CpGs.Author SummaryDNA methylation is an important epigenetic mark that contributes to many biological processes including the regulation of gene expression. Genetic variation has been associated with quantitative changes in DNA methylation (meQTLs). We identified thousands of meQTLs using an assay that allowed us to measure methylation levels at around 300 thousand cytosines. We found that meQTLs are enriched with loci that is also associated with quantitative changes in gene expression, DNase I hypersensitivity, PolII occupancy, and a number of histone marks. This suggests that many molecular events are likely regulated in concert. Finally, we found that changes in transcription factor binding as well as transcription factor abundance are associated with changes in DNA methylation near transcription factor binding sites. This work contributes to our understanding of the regulation of DNA methylation in the larger context of gene regulatory landscape.

Expression Level Of A Coagulation Factor Gene, F13A1 Defines Characteristic Subpopulations Of Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4888-4888
Author(s):  
Csongor Kiss ◽  
Katalin Gyurina ◽  
Gábor Kiss ◽  
Silvia Bresolin ◽  
Zsuzsa Hevessy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Tyrosine Kinases ◽  
Lymphoblastic Leukemia ◽  
Coagulation Factor ◽  
Expression Level ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Using multiparameter flow cytometry, Western blot, ELISA and laser scanning microscopy, leukemic B-cell progenitor lymphoblasts were identified as a novel expression site of coagulation factor XIII subunit A (FXIIIA) (Kiss et al Thromb Haemost 2006). Three-year overall survival (OS) of children with FXIIIA-positive acute lymphoblastic leukemia (ALL) was significantly higher (87%) than 3-yr OS of patients with FXIIIA-negative ALL (65%). Here we report on gene expression profiles (GEP) associated with FXIIIA-positive vs. FXIIIA–negative childhood (ch)ALL. Finnally, the expression levels of F13A1 gene in cytogenetic subgroups were investigated. GEP of 11 FXIIIA-positive and 9 FXIIIA-negative samples of patients treated at the Department of Hematology-Oncology, University of Debrecen was investigated using HG-U 133 plus 2.0 Affymetrix Platform Array. Expression sequence tags (EST) characterized by expression levels with at least 2 logs difference among FXIIIA-positive vs. FXIIIA-negative samples were selected and validated with real-time quantitative PCR. Extending the analysis, we have searched the database containing GEPs of 317 children with ALL treated at the Division of Hemato-Oncology, Department of Women’s and Children’s Health, University of Padova, using R package and Partek Genomic Suite softwares. FXIIIA-positive and FXIIIA-negative samples exhibited a characteristically different GEP. In the FXIIIA-positive samples one of the overexpressed genes was F13A1. FXIIIA-negative samples contained two characteristic groups of overexpressed genes. One of these consisted of genes participating in B-cell development: EBF1, IKZF1 and PAX5. The second set consisted of genes encoding for tyrosine kinases: JAK1, JAK3, NC07523, NC08002, NC06523, NC08345 and for serine-threonine kinase NC00027. In contrast, FXIIIA-positive samples contained only two overexpressed tyrosine kinases: C-KIT and JAK2. A wide variation of F13A1 expression levels of the 317 Padova patients was observed. Since expression level of FXIIIA protein of these patients has not been determined, we have arbitrarily defined F13A1 gene expression levels below 106 as “low” and gene expression levels exceeding 109 as “high”. Considering these two groups, we have investigated the distribution of F13A1 expression among the known cytogenetic subgroups of ALL. Low F13A1 expression was prevalent among “B-other” samples, high F13A1 expression was associated with t(1;19). The pattern of overexpressed ESTs, accumulation of low F13A1 expressing samples in the “B-other” cytogenetic group of ALL and the unfavorable disease outcome of FXIIIA-negative cases may suggest a possible overlap between FXIIIA-negative ALL and BCR-ABL1-like ALL identified recently in the “B-other” group. The nature and extent of this overlap will be investigated prospectively in the BFM ALL-IC 2009 clinical trial. In contrast, high expression levels of F13A1 accumulated preferentially within the t(1;19) genetic group, associated with a good prognosis. Detection of FXIIIA expression by flow cytometry may offer an easy and non-expensive tool for defining new prognostic subpopulations of ALL. Grant support TÁMOP 4.2.2.A-11/1/KONV-2012-0025 project (CK, KG, HZ, IG, IS and JK). The project is co-financed by the European Union and the European Social Fund and the AIRC (Associazione Italiana Ricerca su Cancro; SB) project. Disclosures: No relevant conflicts of interest to declare.

Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels of human gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15669-e15669
Author(s):  
H. Uetake ◽  
K. Shitara ◽  
K. Sugihara
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cancer Cells ◽  
Gene Expression Level ◽  
Expression Level ◽  
Human Gastric Cancer ◽  
Rt Pcr ◽  
Cox 2 ◽  
Laser Capture ◽  
Gene Expression Levels

e15669 Background: We reported the efficacy of laser capture microdissection plus RT-PCR (LCM+RT-PCR) technique in analyzing gene expression levels of human colon cancer (Makino, BMC cancer, 2008). In the present study, gene expression level of angiogenic factors, such as vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cyclooxygenase-2 (COX-2) in human gastric cancer was studies using LCM+RT-PCR methods. Methods: Gene expression level of VEGF, TP and COX-2 were separately quantified in cancer cells and in cancerous stroma of 51 gastric cancers specimen by LCM+RT-PCR methods (Danenberg Tumor Profile). Results: All the gene expressions were successfully estimated separately in cancer cells and cancerous stroma. VEGF and TP gene higher expressed in cancer cell than in cancerous stroma (P<0.0001, Wilcoxon), whereas COX-2 gene expression was higher in cancerous stroma (P=0.0004, Wilcoxon). Only in TP, positive correlation of gene expression was observed between in cancer cells and in cancerous stroma (rs=0.494, P=0.0014, Spearman). And a linear relationship was observed between VEGF and TP gene expression in cancerous stroma (rs=0.768, P<0.0001, Spearman). Conclusions: Gene expression level of angiogenic factor was different between in cancer cells and cancerous stroma. By using LCM+RT-PCR method, gene expression level of angiogenic factors can be separately estimated in cancer cells and cancerous stroma. No significant financial relationships to disclose.

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