scholarly journals Cis-regulatory elements within TEs can influence expression of nearby maize genes

2020 ◽  
Author(s):  
Jaclyn M Noshay ◽  
Alexandre P Marand ◽  
Sarah N Anderson ◽  
Peng Zhou ◽  
Maria Katherine Mejia Guerra ◽  
...  
Keyword(s):  
Allelic Variation ◽  
Regulatory Elements ◽  
Data Availability ◽  
Transcriptional Responses ◽  
Maize Genotypes ◽  
Show Evidence ◽  
The Many ◽  
Dna Regulatory Elements ◽  
Accessible Chromatin ◽  
Eukaryotic Genomes

AbstractTransposable elements (TEs) have the potential to create regulatory variation both through disruption of existing DNA regulatory elements and through creation of novel DNA regulatory elements. In a species with a large genome, such as maize, the many TEs interspersed with genes creates opportunities for significant allelic variation due to TE presence/absence polymorphisms among individuals. We used information on putative regulatory elements in combination with knowledge about TE polymorphisms in maize to identify TE insertions that interrupt existing accessible chromatin regions (ACRs) in B73 as well as examples of polymorphic TEs that contain ACRs among four inbred lines of maize including B73, Mo17, W22, and PH207. The TE insertions in three other assembled maize genomes (Mo17, W22 or PH207) that interrupt ACRs that are present in the B73 genome can trigger changes to the chromatin suggesting the potential for both genetic and epigenetic influences of these insertions. Nearly 20% of the ACRs located over 2kb from the nearest gene are located within an annotated TE. These are regions of unmethylated DNA that show evidence for functional importance similar to ACRs that are not present within TEs. Using a large panel of maize genotypes we tested if there is an association between the presence of TE insertions that interrupt, or carry, an ACR and the expression of nearby genes. TEs that carry ACRs exhibit an enrichment for being associated with higher expression of nearby genes, suggesting that these TEs may create novel regulatory elements. These analyses highlight the potential for TEs to rewire transcriptional responses in eukaryotic genomes.Data AvailabilityIn this study we utilize previously published datasets that are available through the following accessions: SRX4727413, SRR8738272, and SRR8740852.

scholarly journals Assessing the regulatory potential of transposable elements using chromatin accessibility profiles of maize transposons

Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Jaclyn M Noshay ◽  
Alexandre P Marand ◽  
Sarah N Anderson ◽  
Peng Zhou ◽  
Maria Katherine Mejia Guerra ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Allelic Variation ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Transcriptional Responses ◽  
Maize Genotypes ◽  
Show Evidence ◽  
Regulatory Potential ◽  
Dna Regulatory Elements ◽  
Accessible Chromatin

Abstract Transposable elements (TEs) have the potential to create regulatory variation both through the disruption of existing DNA regulatory elements and through the creation of novel DNA regulatory elements. In a species with a large genome, such as maize, many TEs interspersed with genes create opportunities for significant allelic variation due to TE presence/absence polymorphisms among individuals. We used information on putative regulatory elements in combination with knowledge about TE polymorphisms in maize to identify TE insertions that interrupt existing accessible chromatin regions (ACRs) in B73 as well as examples of polymorphic TEs that contain ACRs among four inbred lines of maize including B73, Mo17, W22, and PH207. The TE insertions in three other assembled maize genomes (Mo17, W22, or PH207) that interrupt ACRs that are present in the B73 genome can trigger changes to the chromatin, suggesting the potential for both genetic and epigenetic influences of these insertions. Nearly 20% of the ACRs located over 2 kb from the nearest gene are located within an annotated TE. These are regions of unmethylated DNA that show evidence for functional importance similar to ACRs that are not present within TEs. Using a large panel of maize genotypes, we tested if there is an association between the presence of TE insertions that interrupt, or carry, an ACR and the expression of nearby genes. While most TE polymorphisms are not associated with expression for nearby genes, the TEs that carry ACRs exhibit enrichment for being associated with higher expression of nearby genes, suggesting that these TEs may contribute novel regulatory elements. These analyses highlight the potential for a subset of TEs to rewire transcriptional responses in eukaryotic genomes.

scholarly journals A scalable platform for the development of cell-type-specific viral drivers

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sinisa Hrvatin ◽  
Christopher P Tzeng ◽  
M Aurel Nagy ◽  
Hume Stroud ◽  
Charalampia Koutsioumpa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heterologous Gene Expression ◽  
High Specificity ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Cell Type Specific ◽  
The Many ◽  
Dna Regulatory Elements

Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.

scholarly journals Transposable Elements and Teleost Migratory Behaviour

2021 ◽  
Vol 22 (2) ◽  
pp. 602
Author(s):  
Elisa Carotti ◽  
Federica Carducci ◽  
Adriana Canapa ◽  
Marco Barucca ◽  
Samuele Greco ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Environmental Changes ◽  
Chromosomal Rearrangements ◽  
Quantitative Difference ◽  
Regulatory Elements ◽  
Phylogenetic Position ◽  
Migratory Behaviour ◽  
Relative Contribution ◽  
Migratory Routes ◽  
Eukaryotic Genomes

Transposable elements (TEs) represent a considerable fraction of eukaryotic genomes, thereby contributing to genome size, chromosomal rearrangements, and to the generation of new coding genes or regulatory elements. An increasing number of works have reported a link between the genomic abundance of TEs and the adaptation to specific environmental conditions. Diadromy represents a fascinating feature of fish, protagonists of migratory routes between marine and freshwater for reproduction. In this work, we investigated the genomes of 24 fish species, including 15 teleosts with a migratory behaviour. The expected higher relative abundance of DNA transposons in ray-finned fish compared with the other fish groups was not confirmed by the analysis of the dataset considered. The relative contribution of different TE types in migratory ray-finned species did not show clear differences between oceanodromous and potamodromous fish. On the contrary, a remarkable relationship between migratory behaviour and the quantitative difference reported for short interspersed nuclear (retro)elements (SINEs) emerged from the comparison between anadromous and catadromous species, independently from their phylogenetic position. This aspect is likely due to the substantial environmental changes faced by diadromous species during their migratory routes.

scholarly journals Considerations when investigating lncRNA function in vivo

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Andrew R Bassett ◽  
Asifa Akhtar ◽  
Denise P Barlow ◽  
Adrian P Bird ◽  
Neil Brockdorff ◽  
...  
Keyword(s):  
Normal Cell ◽  
Regulatory Elements ◽  
Genomic Locus ◽  
Cellular Processes ◽  
Cell Processes ◽  
Non Coding Rnas ◽  
Per Se ◽  
Dna Regulatory Elements

Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans-effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of lncRNAs in the light of different models of lncRNA molecular mechanism, and reflect on the design of experiments to mutate lncRNA loci. These considerations should assist in the further investigation of these transcriptional products of the genome.

scholarly journals Highly conserved transcriptional responses to mechanical ventilation of the lung

2010 ◽  
Vol 42 (3) ◽  
pp. 384-396 ◽  
Author(s):  
Kenneth S. Kompass ◽  
Gaetan Deslee ◽  
Carla Moore ◽  
Donald McCurnin ◽  
Richard A. Pierce
Keyword(s):  
Mechanical Ventilation ◽  
Transcription Factors ◽  
Side Effects ◽  
Microarray Data ◽  
Regulatory Elements ◽  
Tissue Growth ◽  
Transcriptional Responses ◽  
Baboon Model ◽  
Additional Control ◽  
Valuable Treatment

Cross-species analysis of microarray data has shown improved discriminating power between healthy and diseased states. Computational approaches have proven effective in deciphering the complexity of human disease by identifying upstream regulatory elements and the transcription factors that interact with them. Here we used both methods to identify highly conserved transcriptional responses during mechanical ventilation, an important therapeutic treatment that has injurious side effects. We generated control and ventilated whole lung samples from the premature baboon model of bronchopulmonary dysplasia (BPD), processed them for microarray, and combined them with existing whole lung oligonucleotide microarray data from 85 additional control samples from mouse, rat, and human and 19 additional ventilated samples from mouse and rat. Of the 2,531 orthologs shared by all 114 samples, 60 were modulated by mechanical ventilation [false discovery rate (FDR)-adjusted q value ( qFDR) = 0.005, ANOVA]. These included transcripts encoding the transcription factors ATF3 and FOS. Because of compelling known roles for these transcription factors, we used computational methods to predict their targets in the premature baboon model of BPD, which included elastin (ELN), gastrin-releasing polypeptide (GRP), and connective tissue growth factor (CTGF). This approach identified highly conserved transcriptional responses to mechanical ventilation and may facilitate identification of therapeutic targets to reduce the side effects of this valuable treatment.

scholarly journals A Common Motif within the Negative Regulatory Regions of Multiple Factors Inhibits Their Transcriptional Synergy

2000 ◽  
Vol 20 (16) ◽  
pp. 6040-6050 ◽  
Author(s):  
Jorge A. Iñiguez-Lluhí ◽  
David Pearce
Keyword(s):  
Binding Sites ◽  
Regulatory Elements ◽  
General Mechanism ◽  
Proper Function ◽  
Protein Motif ◽  
Regulatory Regions ◽  
Response Elements ◽  
Common Motif ◽  
Single Response ◽  
Dna Regulatory Elements

ABSTRACT DNA regulatory elements frequently harbor multiple recognition sites for several transcriptional activators. The response mounted from such compound response elements is often more pronounced than the simple sum of effects observed at single binding sites. The determinants of such transcriptional synergy and its control, however, are poorly understood. Through a genetic approach, we have uncovered a novel protein motif that limits the transcriptional synergy of multiple DNA-binding regulators. Disruption of these conserved synergy control motifs (SC motifs) selectively increases activity at compound, but not single, response elements. Although isolated SC motifs do not regulate transcription when tethered to DNA, their transfer to an activator lacking them is sufficient to impose limits on synergy. Mechanistic analysis of the two SC motifs found in the glucocorticoid receptor N-terminal region reveals that they function irrespective of the arrangement of the receptor binding sites or their distance from the transcription start site. Proper function, however, requires the receptor's ligand-binding domain and an engaged dimer interface. Notably, the motifs are not functional in yeast and do not alter the effect of p160 coactivators, suggesting that they require other nonconserved components to operate. Many activators across multiple classes harbor seemingly unrelated negative regulatory regions. The presence of SC motifs within them, however, suggests a common function and identifies SC motifs as critical elements of a general mechanism to modulate higher-order interactions among transcriptional regulators.

scholarly journals MtrA regulation of essential peptidoglycan cleavage in Mycobacterium tuberculosis during infection

2021 ◽  
Author(s):  
Eliza J. R. Peterson ◽  
Aaron N Brooks ◽  
David J. Reiss ◽  
Amardeep Kaur ◽  
Wei-Ju Wu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Regulatory Elements ◽  
Wide Distribution ◽  
Regulatory Control ◽  
Transcriptional Responses ◽  
Pathogenic Organism ◽  
Rifampicin Treatment ◽  
Genome Wide ◽  
Gene Regulatory Elements ◽  
Dynamic Interplay

AbstractThe success of Mycobacterium tuberculosis (Mtb) is largely due to its ability to withstand multiple stresses encountered in the host. Here, we present a data-driven model that captures the dynamic interplay of environmental cues and genome-encoded regulatory programs in Mtb. The model captures the genome-wide distribution of cis-acting gene regulatory elements and the conditional influences of transcription factors at those elements to elicit environment-specific responses. Analysis of transcriptional responses that may be essential for Mtb to survive acidic stress within the maturing macrophage, identified regulatory control by the MtrAB two-component signal system. Using genome-wide transcriptomics as well as imaging studies, we have characterized the MtrAB circuit by tunable CRISPRi knockdown in both Mtb and the non-pathogenic organism, M. smegmatis (Msm). These experiments validated the essentiality of MtrA in Mtb, but not Msm. We identified that MtrA regulates multiple enzymes that cleave cell wall peptidoglycan and is required for efficient cell division. Moreover, our results suggest that peptidoglycan cleavage, regulated by MtrA, is necessary for Mtb to survive intracellular stress. Further, we present MtrA as an attractive drug target, as even weak repression of mtrA results in loss of Mtb viability and completely clears the bacteria with low-dose isoniazid or rifampicin treatment.

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 Safety Impacts of Converting Two-Way Left-Turn Lanes to Raised Medians and Associated Design Concerns

2016 ◽  
Author(s):  
Priyanka Alluri ◽  
Albert Gan ◽  
Kirolos Haleem
Keyword(s):  
Data Availability ◽  
Left Turn ◽  
Arterial Streets ◽  
Crash Data ◽  
Potential Safety ◽  
Before And After ◽  
Show Evidence ◽  
Crash Types ◽  
Associated Design ◽  
Urban Arterial

Raised medians and two-way left-turn lanes (TWLTLs) are the two most common types of median treatments on arterial streets. This paper aims to conduct a detailed study on the safety impacts of conversion from TWLTLs to raised medians on state roads in Florida. In addition, the study also investigated several potential safety concerns related to raised medians on state roads, including crashes at median openings, vehicles directly hitting the median curb, and median crossover crashes. Based on data availability, 17.51 miles of urban arterial sections in Florida that were converted from TWLTLs to raised medians were analyzed. Police reports of all the crashes before and after median conversion were reviewed to correct miscoded crash types and obtain additional detailed crash information. Overall, a 28.5% reduction in total crash rate was observed after the 10 study locations were converted from TWLTLs to raised medians. The reductions in the proportions of left-turn and right-turn crashes were statistically significant, while the changes in the proportions of other crash types were not statistically significant. Furthermore, the crash data did not show evidence that raised medians are an additional hazard compared with TWLTLs.

scholarly journals Genome-Wide Systematic Characterization of the NPF Family Genes and Their Transcriptional Responses to Multiple Nutrient Stresses in Allotetraploid Rapeseed

2020 ◽  
Vol 21 (17) ◽  
pp. 5947 ◽  
Author(s):  
Hao Zhang ◽  
Shuang Li ◽  
Mengyao Shi ◽  
Sheliang Wang ◽  
Lei Shi ◽  
...  
Keyword(s):  
N Uptake ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Peptide Transporter ◽  
Future Research ◽  
Whole Genome ◽  
Transcriptional Responses ◽  
Ammonium Toxicity ◽  
Genome Wide

NITRATE TRANSPORTER 1 (NRT1)/PEPTIDE TRANSPORTER (PTR) family (NPF) proteins can transport various substrates, and play crucial roles in governing plant nitrogen (N) uptake and distribution. However, little is known about the NPF genes in Brassica napus. Here, a comprehensive genome-wide systematic characterization of the NPF family led to the identification of 193 NPF genes in the whole genome of B. napus. The BnaNPF family exhibited high levels of genetic diversity among sub-families but this was conserved within each subfamily. Whole-genome duplication and segmental duplication played a major role in BnaNPF evolution. The expression analysis indicated that a broad range of expression patterns for individual gene occurred in response to multiple nutrient stresses, including N, phosphorus (P) and potassium (K) deficiencies, as well as ammonium toxicity. Furthermore, 10 core BnaNPF genes in response to N stress were identified. These genes contained 6–13 transmembrane domains, located in plasma membrane, that respond discrepantly to N deficiency in different tissues. Robust cis-regulatory elements were identified within the promoter regions of the core genes. Taken together, our results suggest that BnaNPFs are versatile transporters that might evolve new functions in B. napus. Our findings benefit future research on this gene family.

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