scholarly journals 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Polychlorinated Biphenyl Coexposure Alters the Expression Profile of MicroRNAs in the Liver Associated with Atherosclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qiuli Shan ◽  
Fan Qu ◽  
Ningning Chen
Keyword(s):  
Small Rnas ◽  
Polychlorinated Biphenyl ◽  
System Development ◽  
Complex Mixtures ◽  
Regulate Gene Expression ◽  
Significant Expression ◽  
And Function ◽  
Function Network ◽  
Regulate Gene

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that exist as complex mixtures in vivo. When humans are simultaneously exposed to these compounds, the development of atherosclerosis is known to be enhanced. However, the roles of miRNA in TCDD- and PCB-induced atherosclerosis are largely unknown. Therefore, the present study is aimed at elucidating the possible dysregulation of miRNAs in atherogenesis induced by coexposure to TCDD and PCBs. Eight-week-old male ApoE-/- mice were coexposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) by intraperitoneal injection four times over a 6-week period. Microarray analysis of miRNAs and mRNAs in the liver of ApoE-/- mice with or without TCDD and Aroclor1254 coexposure was performed. We discovered that 68 miRNAs and 1312 mRNAs exhibited significant expression changes in response to TCDD and PCB coexposure and revealed that both changed miRNAs and mRNAs are involved in cardiovascular disease processes. An integrated miRNA-mRNA approach indicated that miRNA-26a-5p, miRNA-193a-3p, and miRNA-30c-5p participated in specific TCDD and Aroclor1254 coresponsive networks which are relevant to the cardiovascular system development and function network. Furthermore, our results also indicated that miRNA-130a-3p and miRNA-376a-3p were novel players in the regulation of TCDD- and Aroclor1254-induced atherosclerosis pathways. In summary, our finding provided new insights into the mechanism of atherosclerosis in response to TCDD and PCB coexposure.

Epigenetherapy, a new concept

2011 ◽  
Vol 2 (3) ◽  
pp. 127-134
Author(s):  
Tiia Husso ◽  
Mikko P. Turunen ◽  
Nigel Parker ◽  
Seppo Ylä-Herttuala
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Basic Research ◽  
Clinical Applications ◽  
Regulate Gene Expression ◽  
Endogenous Gene ◽  
Rna Molecules ◽  
Regulate Gene

AbstractSmall RNAs have been shown to regulate gene transcription by interacting with the promoter region and modifying the histone code. The exact mechanism of function is still unclear but the feasibility to activate or repress endogenous gene expression with small RNA molecules has already been demonstrated in vitro and in vivo. In traditional gene therapy non-mutated or otherwise useful genes are inserted into patient's cells to treat a disease. In epigenetherapy the action of small RNAs is utilized by delivering only the small RNAs to patient's cells where they then regulate gene expression by epigenetic mechanisms. This method could be widely useful not only for basic research but also for clinical applications of small RNAs.

scholarly journals Enhancers Predominantly Regulate Gene Expression in vivo Via Transcription Initiation

2019 ◽  
Author(s):  
Martin Stephen Charles Larke ◽  
Takayuki Nojima ◽  
Jelena Telenius ◽  
Jacqueline A. Sharpe ◽  
Jacqueline A. Sloane-Stanley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Regulate Gene Expression ◽  
Regulate Gene

scholarly journals Small RNAs with 5′-Polyphosphate Termini Associate with a Piwi-Related Protein and Regulate Gene Expression in the Single-Celled Eukaryote Entamoeba histolytica

2008 ◽  
Vol 4 (11) ◽  
pp. e1000219 ◽  
Author(s):  
Hanbang Zhang ◽  
Gretchen M. Ehrenkaufer ◽  
Justine M. Pompey ◽  
Jason A. Hackney ◽  
Upinder Singh
Keyword(s):  
Gene Expression ◽  
Entamoeba Histolytica ◽  
Small Rnas ◽  
Related Protein ◽  
Regulate Gene Expression ◽  
Regulate Gene

scholarly journals Dietary microRNA—A Novel Functional Component of Food

2019 ◽  
Vol 10 (4) ◽  
pp. 711-721 ◽  
Author(s):  
Lin Zhang ◽  
Ting Chen ◽  
Yulong Yin ◽  
Chen-Yu Zhang ◽  
Yong-Liang Zhang
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Biological Significance ◽  
Circulatory System ◽  
Physiological Effects ◽  
Biological Processes ◽  
Regulate Gene Expression ◽  
Functional Component ◽  
Health And Disease ◽  
Regulate Gene

ABSTRACT MicroRNAs are a class of small RNAs that play essential roles in various biological processes by silencing genes. Evidence emerging in recent years suggests that microRNAs in food can be absorbed into the circulatory system and organs of humans and other animals, where they regulate gene expression and biological processes. These food-derived dietary microRNAs may serve as a novel functional component of food, a role that has been neglected to date. However, a significant amount of evidence challenges this new concept. The absorption, stability, and physiological effects of dietary microRNA in recipients, especially in mammals, are currently under heavy debate. In this review, we summarize our current understanding of the unique characteristics of dietary microRNAs and concerns about both the mechanistic and methodological basis for studying the biological significance of dietary microRNAs. Such efforts will benefit continuing investigations and offer new perspectives for the interpretation of the roles of dietary microRNA with respect to the health and disease of humans and animals.

248 DIESTRUS TRANSCRIPTOME DYNAMICS OF BOVINE ENDOMETRIUM IN RELATION TO PREGNANCY SUCCESS AFTER EMBRYO TRANSFER

2010 ◽  
Vol 22 (1) ◽  
pp. 281
Author(s):  
D. Salilew-Wondim ◽  
N. Ghanem ◽  
M. Hoelker ◽  
F. Rings ◽  
C. Phatsara ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Embryo Transfer ◽  
System Development ◽  
Mapk Signaling ◽  
Nervous System Development ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Transferase Activity ◽  
And Function

This experiment aimed to investigate the diestrus transcriptome dynamics of endometrium that resulted in calf delivery or no pregnancy after embryo transfer. Endometrium biopsies were collected from Simmental cyclic heifers at Days 7 and 14 of estrus cycle. On the next cycle, in vivo-produced Day 7 blastocysts were transferred to all animals at Day 7 of estrous cycle. Following pregnancy diagnosis, the endometrial biopsies collected at Day 7 and 14 were categorized based on the pregnancy success. Those endometrial biopsies collected from heifers that subsequently delivered a calf were assigned to the calf-delivery group, and those collected from heifers that did not conceive were assigned to the no-pregnancy group. The endometrial temporal transcriptome profile was compared between Days 7 and 14 in both heifer groups. Total RNA was isolated from each sample in triplicate. Two rounds of RNA amplification were performed using MEGAscript® T7 Kit (Ambion, Inc., Austin, TX, USA) and GeneChip® IVT Labeling Kit (Affymetrix, Inc., Santa Clara, CA, USA), respectively. Following fragmentation, biotin-labeled cRNA samples were hybridized to Affymetrix bovine gene chip array. The microarray data normalization and background correction were performed using GCRMA, and the differentially expressed genes (DEG) (fold change >2,P < 0.05, FDR < 0.3) were identified using LIMMA written on R package integrated with Bioconductor. The result showed that in the calf-delivery group, there were 1867 DEG, among which 1015 and 852 were up- and down-regulated, respectively, in Day 7 compared with Day 14 of the estrous cycle. Some of those genes are believed to be involved in reproductive system development and function (F3, PTGER2, PTGER4, MFGE8, PTGS2, and TDGF1), embryonic development (ALDH1A1,ALDH1A3, FGF2, TGFBR2, PDGFB, and TGFBR2), and nervous system development and function (CYP3A4, CYP3A4, HSD17B4, FOXA2, MET, TDGF, WNT11). The bioinformatic analysis using KEGG revealed that those DEG were classified into several pathways including the MAPK signaling pathway. On the other hand, in the no-pregnancy group, 254 genes were found to be differentially expressed, of which 160 and 94 were up- and down-regulated, respectively, in Day 7 compared with Day 14 of the estrous cycle. Some of these genes were found to be involved in signal transducer activity (AXIN2, AGTR1, MAPK10, NTRK2, TLR2, DMBT1, IL1RN, CDK5, CHRNE), transferase activity (DGKI, TXNDC6, RPS6KA5, RIOK3, MYLK, CDK5, MET, NTRK2), receptor activity (MET,AGTR1, NTRK2, TLR2, DMBT1, CHRNE), regulation of transcription (FOS, ELF1, BHLHB2,ATF3, HOXA11), signal transduction (TLR2, AGTR1, FCNB, DGK, NOTCH2, ADAM9, PLEK), and transcription regulator activity (BHLHB2, FOS, ELF1,ATF3, HOXA11). Those DEG were found to be involved in different pathways including the focal adhesion pathway. In conclusion, the result of the current study revealed a remarkable transcriptome dynamics between Days 7 and 14 of the estrous cycle in cows resulted in calf delivery compared with those that did not support pregnancy.

scholarly journals In vivo differences between endothelial transcriptional profiles of coronary and iliac arteries revealed by microarray analysis

2008 ◽  
Vol 295 (4) ◽  
pp. H1556-H1561 ◽  
Author(s):  
Ji Zhang ◽  
Kelley A. Burridge ◽  
Morton H. Friedman
Keyword(s):  
Dna Microarrays ◽  
System Development ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Profiles ◽  
Classical Pathway ◽  
Biological Pathway Analysis ◽  
Almost All ◽  
And Function

Endothelial cells (ECs) from different vascular beds display a remarkable heterogeneity in both structure and function. Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity between typical atheroprone and atheroresistant arteries, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary (CECs) and iliac artery (IECs) ECs. Statistical analysis revealed 51 genes that were differentially expressed in CECs relative to IECs at a false discovery rate of 5%. Seventeen of these genes are known to be involved in atherogenesis. Consistent with coronary arteries being more atherosusceptible, almost all putative atherogenic genes were overexpressed in CECs, whereas all atheroprotective genes were downregulated, relative to IECs. A subset of the identified genes was validated by quantitative polymerase chain reaction (PCR). PCR results suggest that the differences in expression levels between CECs and IECs for the HOXA10 and HOXA9 genes were >100-fold. Gene ontology (GO) and biological pathway analysis revealed a global expression difference between CECs and IECs. Genes in twelve GO categories, including complement immune activation, immunoglobulin-mediated response, and system development, were significantly upregulated in CECs. CECs also overexpressed genes involved in several inflammatory pathways, including the classical pathway of complement activation and the IGF-1-mediated pathway. The in vivo transcriptional differences between CECs and IECs found in this study may provide new insights into the factors responsible for coronary artery atherosusceptibility.

scholarly journals A multiplexed, automated evolution pipeline enables scalable discovery and characterization of biosensors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Brent Townshend ◽  
Joy S. Xiang ◽  
Gabriel Manzanarez ◽  
Eric J. Hayden ◽  
Christina D. Smolke
Keyword(s):  
Small Molecules ◽  
Biosynthetic Pathway ◽  
De Novo ◽  
Living Cells ◽  
Regulate Gene Expression ◽  
Liquid Handling ◽  
Regulate Gene

AbstractBiosensors are key components in engineered biological systems, providing a means of measuring and acting upon the large biochemical space in living cells. However, generating small molecule sensing elements and integrating them into in vivo biosensors have been challenging. Here, using aptamer-coupled ribozyme libraries and a ribozyme regeneration method, de novo rapid in vitro evolution of RNA biosensors (DRIVER) enables multiplexed discovery of biosensors. With DRIVER and high-throughput characterization (CleaveSeq) fully automated on liquid-handling systems, we identify and validate biosensors against six small molecules, including five for which no aptamers were previously found. DRIVER-evolved biosensors are applied directly to regulate gene expression in yeast, displaying activation ratios up to 33-fold. DRIVER biosensors are also applied in detecting metabolite production from a multi-enzyme biosynthetic pathway. This work demonstrates DRIVER as a scalable pipeline for engineering de novo biosensors with wide-ranging applications in biomanufacturing, diagnostics, therapeutics, and synthetic biology.

scholarly journals The yeast SWI-SNF complex facilitates binding of a transcriptional activator to nucleosomal sites in vivo.

1997 ◽  
Vol 17 (8) ◽  
pp. 4811-4819 ◽  
Author(s):  
L G Burns ◽  
C L Peterson
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Protein Assembly ◽  
Transcriptional Activators ◽  
Regulate Gene Expression ◽  
Activation Of Transcription ◽  
Free Region ◽  
And Function

The Saccharomyces cerevisiae SWI-SNF complex is a 2-MDa protein assembly that is required for the function of many transcriptional activators. Here we describe experiments on the role of the SWI-SNF complex in activation of transcription by the yeast activator GAL4. We find that while SWI-SNF activity is not required for the GAL4 activator to bind to and activate transcription from nucleosome-free binding sites, the complex is required for GAL4 to bind to and function at low-affinity, nucleosomal binding sites in vivo. This SWI-SNF dependence can be overcome by (i) replacing the low-affinity sites with higher-affinity, consensus GAL4 binding sequences or (ii) placing the low-affinity sites into a nucleosome-free region. These results define the criteria for the SWI-SNF dependence of gene expression and provide the first in vivo evidence that the SWI-SNF complex can regulate gene expression by modulating the DNA binding of an upstream activator protein.

scholarly journals Interplay between MITF, PIAS3, and STAT3 in Mast Cells and Melanocytes

2004 ◽  
Vol 24 (24) ◽  
pp. 10584-10592 ◽  
Author(s):  
Amir Sonnenblick ◽  
Carmit Levy ◽  
Ehud Razin
Keyword(s):  
Mast Cells ◽  
Mrna Levels ◽  
3T3 Cells ◽  
Regulate Gene Expression ◽  
Gp130 Receptor ◽  
Microphthalmia Transcription Factor ◽  
And Function ◽  
Nih 3T3 ◽  
Regulation Of Growth

ABSTRACT Microphthalmia transcription factor (MITF) and STAT3 are two transcription factors that play a major role in the regulation of growth and function in mast cells and melanocytes. In the present study, we explored the MITF-PIAS3-STAT3 network of interactions, how these interactions regulate gene expression, and how cytokine-mediated phosphorylation of MITF and STAT3 is involved in the in vivo interplay between these three proteins. In NIH 3T3 cells stimulated via gp130 receptor, transfected MITF was found to be phosphorylated at S409. Such phosphorylation of MITF leads to PIAS3 dissociation from MITF and its association with STAT3. Activation of mouse melanoma and mast cells through gp130 or c-Kit receptors induced the mobilization of PIAS3 from MITF to STAT3. In mast cells derived from MITF di/di mice, whose MITF lacks the Zip domain (PIAS3-binding domain), we found downregulation in mRNA levels of genes regulated by either MITF or STAT3. This regulatory mechanism is of considerable importance since it is likely to advance the deciphering of a role for MITF and STAT3 in mast cells and melanocytes.

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