scholarly journals Role of Non-Coding Regulatory Elements in the Control of GR-Dependent Gene Expression

2021 ◽  
Vol 22 (8) ◽  
pp. 4258
Author(s):  
Malgorzata Borczyk ◽  
Mateusz Zieba ◽  
Michał Korostyński ◽  
Marcin Piechota
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Regulatory Elements ◽  
Transcription Activator ◽  
Long Distance ◽  
Core Promoters ◽  
Transcriptional Changes ◽  
Gene Expression Dynamics ◽  
Upregulated Genes

The glucocorticoid receptor (GR, also known as NR3C1) coordinates molecular responses to stress. It is a potent transcription activator and repressor that influences hundreds of genes. Enhancers are non-coding DNA regions outside of the core promoters that increase transcriptional activity via long-distance interactions. Active GR binds to pre-existing enhancer sites and recruits further factors, including EP300, a known transcriptional coactivator. However, it is not known how the timing of GR-binding-induced enhancer remodeling relates to transcriptional changes. Here we analyze data from the ENCODE project that provides ChIP-Seq and RNA-Seq data at distinct time points after dexamethasone exposure of human A549 epithelial-like cell line. This study aimed to investigate the temporal interplay between GR binding, enhancer remodeling, and gene expression. By investigating a single distal GR-binding site for each differentially upregulated gene, we show that transcriptional changes follow GR binding, and that the largest enhancer remodeling coincides in time with the highest gene expression changes. A detailed analysis of the time course showed that for upregulated genes, enhancer activation persists after gene expression changes settle. Moreover, genes with the largest change in EP300 binding showed the highest expression dynamics before the peak of EP300 recruitment. Overall, our results show that enhancer remodeling may not directly be driving gene expression dynamics but rather be a consequence of expression activation.

Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression

2004 ◽  
Vol 287 (5) ◽  
pp. H1957-H1966 ◽  
Author(s):  
Faina Schwartz ◽  
Arvi Duka ◽  
Irena Duka ◽  
Jing Cui ◽  
Haralambos Gavras
Keyword(s):  
Gene Expression ◽  
Cardiac Remodeling ◽  
Unknown Function ◽  
Mouse Heart ◽  
Ang Ii ◽  
Coordinate Regulation ◽  
Transcriptional Changes ◽  
Novel Targets ◽  
Molecular Circuitry

Although the central role of ANG II in cardiovascular homeostasis is well appreciated, the molecular circuitry of its many actions is not completely understood. With the use of serial analysis of gene expression to assess global transcriptional changes in the heart of mice after continuous 7-day ANG II administration, we identified patterns of gene expression indicative of cardiac remodeling, including coordinate regulation of genes previously described in a context of processes associated with hypertrophy and fibrosis. In addition, we discovered several novel ANG II targets, including characterized genes of known function, recently annotated genes of unknown function, and the putative genes not yet present in current databases. The serial analysis of gene expression approach to assess the role of ANG II presented in this report provides new venues for inquiries into ANG II-mediated cardiac function.

scholarly journals Identification and classification of cis-regulatory elements in the amphipod crustacean Parhyale hawaiensis

2021 ◽  
Author(s):  
Dennis A Sun ◽  
Nipam H Patel
Keyword(s):  
Gene Expression ◽  
Genome Annotation ◽  
Time Course ◽  
Regulatory Elements ◽  
Rna Seq ◽  
Genome Wide ◽  
Long Read ◽  
Amphipod Crustacean ◽  
Accessible Chromatin

AbstractEmerging research organisms enable the study of biology that cannot be addressed using classical “model” organisms. The development of novel data resources can accelerate research in such animals. Here, we present new functional genomic resources for the amphipod crustacean Parhyale hawaiensis, facilitating the exploration of gene regulatory evolution using this emerging research organism. We use Omni-ATAC-Seq, an improved form of the Assay for Transposase-Accessible Chromatin coupled with next-generation sequencing (ATAC-Seq), to identify accessible chromatin genome-wide across a broad time course of Parhyale embryonic development. This time course encompasses many major morphological events, including segmentation, body regionalization, gut morphogenesis, and limb development. In addition, we use short- and long-read RNA-Seq to generate an improved Parhyale genome annotation, enabling deeper classification of identified regulatory elements. We leverage a variety of bioinformatic tools to discover differential accessibility, predict nucleosome positioning, infer transcription factor binding, cluster peaks based on accessibility dynamics, classify biological functions, and correlate gene expression with accessibility. Using a Minos transposase reporter system, we demonstrate the potential to identify novel regulatory elements using this approach, including distal regulatory elements. This work provides a platform for the identification of novel developmental regulatory elements in Parhyale, and offers a framework for performing such experiments in other emerging research organisms.Primary Findings-Omni-ATAC-Seq identifies cis-regulatory elements genome-wide during crustacean embryogenesis-Combined short- and long-read RNA-Seq improves the Parhyale genome annotation-ImpulseDE2 analysis identifies dynamically regulated candidate regulatory elements-NucleoATAC and HINT-ATAC enable inference of nucleosome occupancy and transcription factor binding-Fuzzy clustering reveals peaks with distinct accessibility and chromatin dynamics-Integration of accessibility and gene expression reveals possible enhancers and repressors-Omni-ATAC can identify known and novel regulatory elements

scholarly journals Transcriptional Control of Honey Bee (Apis mellifera) Major Royal Jelly Proteins by 20-Hydroxyecdysone

Insects ◽  
2018 ◽  
Vol 9 (3) ◽  
pp. 122 ◽  
Author(s):  
Paul Winkler ◽  
Frank Sieg ◽  
Anja Buttstedt
Keyword(s):  
Gene Expression ◽  
Apis Mellifera ◽  
Juvenile Hormone ◽  
Honey Bee ◽  
Honey Bees ◽  
Transcriptional Control ◽  
Royal Jelly ◽  
Adult Worker ◽  
Gene Expression Dynamics

One of the first tasks of worker honey bees (Apis mellifera) during their lifetime is to feed the larval offspring. In brief, young workers (nurse bees) secrete a special food jelly that contains a large amount of unique major royal jelly proteins (MRJPs). The regulation of mrjp gene expression is not well understood, but the large upregulation in well-fed nurse bees suggests a tight repression until, or a massive induction upon, hatching of the adult worker bees. The lipoprotein vitellogenin, the synthesis of which is regulated by the two systemic hormones 20-hydroxyecdysone and juvenile hormone, is thought to be a precursor for the production of MRJPs. Thus, the regulation of mrjp expression by the said systemic hormones is likely. This study focusses on the role of 20-hydroxyecdysone by elucidating its effect on mrjp gene expression dynamics. Specifically, we tested whether 20-hydroxyecdysone displayed differential effects on various mrjps. We found that the expression of the mrjps (mrjp1–3) that were finally secreted in large amounts into the food jelly, in particular, were down regulated by 20-hydroxyecdysone treatment, with mrjp3 showing the highest repression value.

scholarly journals The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Song ◽  
Roded Sharan ◽  
Ivan Ovcharenko
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Target Gene ◽  
Regulatory Elements ◽  
Distal Enhancer ◽  
Human Genes ◽  
Multiple Cell ◽  
A Chain ◽  
Target Promoter

Abstract Background Robustness and evolutionary stability of gene expression in the human genome are established by an array of redundant enhancers. Results Using Hi-C data in multiple cell lines, we report a comprehensive map of promoters and active enhancers connected by chromatin contacts, spanning 9000 enhancer chains in 4 human cell lines associated with 2600 human genes. We find that the first enhancer in a chain that directly contacts the target promoter is commonly located at a greater genomic distance from the promoter than the second enhancer in a chain, 96 kb vs. 45 kb, respectively. The first enhancer also features higher similarity to the promoter in terms of tissue specificity and higher enrichment of loop factors, suggestive of a stable primary contact with the promoter. In contrast, a chain of enhancers which connects to the target promoter through a neutral DNA segment instead of an enhancer is associated with a significant decrease in target gene expression, suggesting an important role of the first enhancer in initiating transcription using the target promoter and bridging the promoter with other regulatory elements in the locus. Conclusions The widespread chained structure of gene enhancers in humans reveals that the primary, critical enhancer is distal, commonly located further away than other enhancers. This first, distal enhancer establishes contacts with multiple regulatory elements and safeguards a complex regulatory program of its target gene.

scholarly journals TcpH Influences Virulence Gene Expression in Vibrio cholerae by Inhibiting Degradation of the Transcription Activator TcpP

2004 ◽  
Vol 186 (24) ◽  
pp. 8309-8316 ◽  
Author(s):  
Nancy A. Beck ◽  
Eric S. Krukonis ◽  
Victor J. DiRita
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Time Course ◽  
Virulence Gene ◽  
Degradation Pathway ◽  
Mrna Levels ◽  
Transcription Activator ◽  
Virulence Gene Expression ◽  
Protein Levels ◽  
Periplasmic Domain

ABSTRACT Expression of toxT, the transcription activator of cholera toxin and pilus production in Vibrio cholerae, is the consequence of a complex cascade of regulatory events that culminates in activation of the toxT promoter by TcpP and ToxR, two membrane-localized transcription factors. Both are encoded in operons with genes whose products, TcpH and ToxS, which are also membrane localized, are hypothesized to control their activity. In this study we analyzed the role of TcpH in controlling TcpP function. We show that a mutant of V. cholerae lacking TcpH expressed virtually undetectable levels of TcpP, although tcpP mRNA levels remain unaffected. A time course experiment showed that levels of TcpP, expressed from a plasmid, are dramatically reduced over time without co-overexpression of TcpH. By contrast, deletion of toxS did not affect ToxR protein levels. A fusion protein in which the TcpP periplasmic domain is replaced with that of ToxR remains stable, suggesting that the periplasmic domain of TcpP is the target for degradation of the protein. Placement of the periplasmic domain of TcpP on ToxR, an otherwise stable protein, results in instability, providing further evidence for the hypothesis that the periplasmic domain of TcpP is a target for degradation. Consistent with this interpretation is our finding that derivatives of TcpP lacking a periplasmic domain are more stable in V. cholerae than are derivatives in which the periplasmic domain has been truncated. This work identifies at least one role for the periplasmic domain of TcpP, i.e., to act as a target for a protein degradation pathway that regulates TcpP levels. It also provides a rationale for why the V. cholerae tcpH mutant strain is avirulent. We hypothesize that regulator degradation may be an important mechanism for regulating virulence gene expression in V. cholerae.

scholarly journals Study of Long-Distance Functional Interactions between Su(Hw) Insulators That Can Regulate Enhancer-Promoter Communication in Drosophila melanogaster

2006 ◽  
Vol 26 (3) ◽  
pp. 754-761 ◽  
Author(s):  
Ekaterina Savitskaya ◽  
Larisa Melnikova ◽  
Margarita Kostuchenko ◽  
Elena Kravchenko ◽  
Ekaterina Pomerantseva ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Relevant Literature ◽  
Regulatory Elements ◽  
Large Set ◽  
Pairing Interaction ◽  
Long Distance ◽  
Control Of Gene Expression ◽  
Functional Interactions ◽  
Enhancer Blocking

ABSTRACT The Su(Hw) insulator found in the gypsy retrotransposon is the most potent enhancer blocker in Drosophila melanogaster. However, two such insulators in tandem do not prevent enhancer-promoter communication, apparently because of their pairing interaction that results in mutual neutralization. Furthering our studies of the role of insulators in the control of gene expression, here we present a functional analysis of a large set of transgenic constructs with various arrangements of regulatory elements, including two or three insulators. We demonstrate that their interplay can have quite different outcomes depending on the order of and distance between elements. Thus, insulators can interact with each other over considerable distances, across interposed enhancers or promoters and coding sequences, whereby enhancer blocking may be attenuated, cancelled, or restored. Some inferences concerning the possible modes of insulator action are made from collating the new data and the relevant literature, with tentative schemes illustrating the regulatory situations in particular model constructs.

scholarly journals Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Loïc Louvet ◽  
Laurent Metzinger ◽  
Janine Büchel ◽  
Sonja Steppan ◽  
Ziad A. Massy
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Inorganic Phosphate ◽  
Time Course ◽  
Mechanistic Explanation ◽  
High Phosphate

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg2+) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg2+on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg2+chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg2+restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg2+. As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg2+with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC.

scholarly journals Combinatorial analysis of Saccharomyces cerevisiae regulatory elements

2019 ◽  
Author(s):  
N. Dhillon ◽  
R. Shelansky ◽  
B. Townshend ◽  
M. Jain ◽  
H. Boeger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Specific Interaction ◽  
Principal Component ◽  
Regulatory Elements ◽  
Untranslated Regions ◽  
Core Promoters ◽  
Regulatory Circuits ◽  
Expression Cluster ◽  
Multiple Levels

AbstractGene expression in Saccharomyces cerevisiae is regulated at multiple levels. Genomic and epigenomic mapping of transcription factors and chromatin components has led to the definition and delineation of various regulatory elements. Enhancers, promoters, 5’ untranslated regions (5’UTR) and transcription terminators/3’ untranslated regions (3’UTR) have all been defined. However, the specific contributions of each of these features as part of a regulatory unit and the functional communications between these regulatory elements remains under explored.We built a combinatorial library of 26 different enhancers, core promoters, 5’UTRs and transcription terminators/3’UTRs. This library was analyzed with respect to gene expression in order to better understand the interactions between different regulatory elements. In the process we developed new methods to estimate the contribution of individual regulatory parts from just a few simple measurements. Our data show that different pairs of regulatory parts follow specific interaction rules affecting overall activity either positively or negatively. We find that while enhancers are the initiators of gene activity, core promoters modulate the levels of enhancer mediated expression. Cluster analysis based on expression show that TATA-box containing core promoters appear to increase enhancer-driven transcription to a greater extent than TATA-less promoters. Principal component analysis highlight outliers and suggest differences in mechanisms of regulation. These results provide a system to characterize regulatory elements and use these elements in the design of synthetic regulatory circuits.

scholarly journals Cilium Expression Score Predicts Glioma Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Srinivas Rajagopalan ◽  
Amartya Singh ◽  
Hossein Khiabanian
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Poor Survival ◽  
Aggressive Tumors ◽  
Regulated Gene Expression ◽  
Upregulated Genes ◽  
Expression Score

The accurate classification, prognostication, and treatment of gliomas has been hindered by an existing cellular, genomic, and transcriptomic heterogeneity within individual tumors and their microenvironments. Traditional clustering is limited in its ability to distinguish heterogeneity in gliomas because the clusters are required to be exclusive and exhaustive. In contrast, biclustering can identify groups of co-regulated genes with respect to a subset of samples and vice versa. In this study, we analyzed 1,798 normal and tumor brain samples using an unsupervised biclustering approach. We identified co-regulated gene expression profiles that were linked to proximally located brain regions and detected upregulated genes in subsets of gliomas, associated with their histologic grade and clinical outcome. In particular, we present a cilium-associated signature that when upregulated in tumors is predictive of poor survival. We also introduce a risk score based on expression of 12 cilium-associated genes which is reproducibly informative of survival independent of other prognostic biomarkers. These results highlight the role of cilia in development and progression of gliomas and suggest potential therapeutic vulnerabilities for these highly aggressive tumors.

scholarly journals Intestinal DCs global gene expression dynamics affected by recombinant baker’s yeasts saccharomyces cerevisiae

2019 ◽  
Author(s):  
Baoquan Han ◽  
Tingting Zhang ◽  
Xinyi Li ◽  
Rui Zhao ◽  
Wei Ge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Inflammatory Response ◽  
Budding Yeast ◽  
Global Gene Expression ◽  
Transcriptome Profile ◽  
Delivery Vehicle ◽  
Gene Delivery Vehicle ◽  
Gene Expression Dynamics

Abstract Background The baker’s yeast, saccharomyces cerevisiae, has been widely used throughout our daily life in diverse aspects for thousands of years. The saccharomyces cerevisiae was found to specifically target the dendritic cells (DCs) in mammalian with a manner of antigen-receptor interaction as described previously. It is necessary to investigate the effect of the baker’s yeasts on global gene expression dynamics of intestinal DCs and explore the possibilities of using baker’s yeast as gene delivery vehicle to modulate animal’s immune functions Results with a murine oral delivery model in vivo, we confirmed the feasibility of using budding yeast as gene delivery vehicle to the intestinal DCs using the Western blots. We then examined the transcriptome profile of the mouse intestinal DCs upon yeast stimulus. The enrichment analysis of unique transcripts indicated the beneficial role of yeast in modulating the DC-mediated adaptive immunity. Compared with previous study, we also found that a large fraction of the regulated genes is coincident with the response induced by other fungus, suggesting that the budding yeast induces a similar tailored unique genetic re-programming of DCs. Another analysis of transcriptome profile indicated that expression of β-catenin gene significantly changes DCs gene expression related to inflammatory response and cell adhesion. Conclusions Here, we defined the role of budding yeast on global gene expression of intestinal DCs, and confirmed the important role of β-catenin gene on the DCs-related inflammatory response, which provides a framework for the development of mucosa yeast-based DNA vaccine.

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