scholarly journals Transcript degradation and codon usage regulate gene expression in a lytic phage

2019 ◽  
Author(s):  
Benjamin R. Jack ◽  
Daniel R. Boutz ◽  
Matthew L. Paff ◽  
Bartram L. Smith ◽  
Claus O. Wilke
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Computational Models ◽  
Regulatory Elements ◽  
Mechanistic Modeling ◽  
Host Cells ◽  
Bacteriophage T7 ◽  
Lytic Phage ◽  
Regulate Gene Expression ◽  
Regulate Gene

AbstractMany viral genomes are small, containing only single- or double-digit numbers of genes and relatively few regulatory elements. Yet viruses successfully execute complex regulatory programs as they take over their host cells. Here, we propose that some viruses regulate gene expression via a carefully balanced interplay between transcription, translation, and transcript degradation. As our model system, we employ bacteriophage T7, whose genome of approximately 60 genes is well annotated and for which there is a long history of computational models of gene regulation. We expand upon prior modeling work by implementing a stochastic gene expression simulator that tracks individual transcripts, polymerases, ribosomes, and RNases participating in the transcription, translation, and transcript-degradation processes occurring during a T7 infection. By combining this detailed mechanistic modeling of a phage infection with high throughput gene expression measurements of several strains of bacteriophage T7, evolved and engineered, we can show that both the dynamic interplay between transcription and transcript degradation, and between these two processes and translation, appear to be critical components of T7 gene regulation. Our results point to a generic gene regulation strategy that may have evolved in many other viruses. Further, our results suggest that detailed mechanistic modeling may uncover the biological mechanisms at work in both evolved and engineered virus variants.

scholarly journals Transcript degradation and codon usage regulate gene expression in a lytic phage†

2019 ◽  
Vol 5 (2) ◽  
Author(s):  
Benjamin R Jack ◽  
Daniel R Boutz ◽  
Matthew L Paff ◽  
Bartram L Smith ◽  
Claus O Wilke
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Computational Models ◽  
Regulatory Elements ◽  
Mechanistic Modeling ◽  
Host Cells ◽  
Bacteriophage T7 ◽  
Lytic Phage ◽  
Regulate Gene Expression ◽  
Regulate Gene

Abstract Many viral genomes are small, containing only single- or double-digit numbers of genes and relatively few regulatory elements. Yet viruses successfully execute complex regulatory programs as they take over their host cells. Here, we propose that some viruses regulate gene expression via a carefully balanced interplay between transcription, translation, and transcript degradation. As our model system, we employ bacteriophage T7, whose genome of approximately sixty genes is well annotated and for which there is a long history of computational models of gene regulation. We expand upon prior modeling work by implementing a stochastic gene expression simulator that tracks individual transcripts, polymerases, ribosomes, and ribonucleases participating in the transcription, translation, and transcript-degradation processes occurring during a T7 infection. By combining this detailed mechanistic modeling of a phage infection with high-throughput gene expression measurements of several strains of bacteriophage T7, evolved and engineered, we can show that both the dynamic interplay between transcription and transcript degradation, and between these two processes and translation, appear to be critical components of T7 gene regulation. Our results point to targeted degradation as a generic gene regulation strategy that may have evolved in many other viruses. Further, our results suggest that detailed mechanistic modeling may uncover the biological mechanisms at work in both evolved and engineered virus variants.

scholarly journals Sensing, Signaling, and Secretion: A Review and Analysis of Systems for Regulating Host Interaction in Wolbachia

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 813 ◽  
Author(s):  
Amelia R. I. Lindsey
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Promising Candidate ◽  
Regulate Gene Expression ◽  
Host Interaction ◽  
Female Germline ◽  
Intracellular Infections ◽  
Regulate Gene

Wolbachia (Anaplasmataceae) is an endosymbiont of arthropods and nematodes that resides within host cells and is well known for manipulating host biology to facilitate transmission via the female germline. The effects Wolbachia has on host physiology, combined with reproductive manipulations, make this bacterium a promising candidate for use in biological- and vector-control. While it is becoming increasingly clear that Wolbachia’s effects on host biology are numerous and vary according to the host and the environment, we know very little about the molecular mechanisms behind Wolbachia’s interactions with its host. Here, I analyze 29 Wolbachia genomes for the presence of systems that are likely central to the ability of Wolbachia to respond to and interface with its host, including proteins for sensing, signaling, gene regulation, and secretion. Second, I review conditions under which Wolbachia alters gene expression in response to changes in its environment and discuss other instances where we might hypothesize Wolbachia to regulate gene expression. Findings will direct mechanistic investigations into gene regulation and host-interaction that will deepen our understanding of intracellular infections and enhance applied management efforts that leverage Wolbachia.

scholarly journals Ribo-attenuators: novel elements for reliable and modular riboswitch engineering

2016 ◽  
Author(s):  
Thomas Folliard ◽  
Barbara Mertins ◽  
Thomas P Prescott ◽  
Harrison Steel ◽  
Thomas Newport ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Molecules ◽  
Regulatory Elements ◽  
Genetic Element ◽  
Regulate Gene Expression ◽  
Considerable Potential ◽  
Expression Variation ◽  
Wide Range ◽  
Genetic Context ◽  
Regulate Gene

AbstractRiboswitches are structural genetic regulatory elements that directly couple the sensing of small molecules to gene expression. They have considerable potential for applications throughout synthetic biology and bio-manufacturing as they are able to sense a wide range of small molecules and regulate gene expression in response. Despite over a decade of research they have yet to reach this considerable potential as they cannot yet be treated as modular components. This is due to several limitations including sensitivity to changes in genetic context, low tunability, and variability in performance. To overcome the associated difficulties with riboswitches, we have designed and introduced a novel genetic element called a Ribo-attenuator in Bacteria. This genetic element allows for predictable tuning, insulation from contextual changes, and a reduction in expression variation. Ribo-attenuators allow riboswitches to be treated as truly modular and tunable components, and thus increases their reliability for a wide range of applications.

scholarly journals Genomic decoding of neuronal depolarization by stimulus-specific NPAS4 heterodimers

2019 ◽  
Author(s):  
G. Stefano Brigidi ◽  
Michael G. B. Hayes ◽  
Andrea L. Hartzell ◽  
Lorane Texari ◽  
Pei-Ann Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Action Potential ◽  
Regulate Gene Expression ◽  
Synaptic Inputs ◽  
Different Types ◽  
Genomic Regulation ◽  
External Stimuli ◽  
Regulate Gene

SUMMARYCells regulate gene expression in response to salient external stimuli. In neurons, depolarization leads to the expression of inducible transcription factors (ITFs) that direct subsequent gene regulation. Depolarization encodes both a neuron’s action potential (AP) output and synaptic inputs, via excitatory postsynaptic potentials (EPSPs). However, it is unclear if different types of depolarizing signals can be transformed by an ITF into distinct modes of genomic regulation. Here, we show that APs and EPSPs in the murine hippocampus trigger two spatially segregated and molecularly distinct mechanisms that lead to the expression of the ITF NPAS4. These two pathways culminate in the assembly of unique, stimulus-specific NPAS4 heterodimers that exhibit distinctive DNA binding patterns. Thus, NPAS4 independently communicates increases in a neuron’s spiking output and synaptic inputs to the nucleus, enabling gene regulation to be tailored to the type of depolarizing activity experienced by a neuron.

scholarly journals CoRE-ATAC: A deep learning model for the functional classification of regulatory elements from single cell and bulk ATAC-seq data

2020 ◽  
Author(s):  
Asa Thibodeau ◽  
Shubham Khetan ◽  
Alper Eroglu ◽  
Ryan Tewhey ◽  
Michael L. Stitzel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Deep Learning ◽  
Immune Cells ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Regulatory Function ◽  
Regulate Gene Expression ◽  
Regulatory Functions ◽  
Regulate Gene

AbstractCis-Regulatory elements (cis-REs) include promoters, enhancers, and insulators that regulate gene expression programs via binding of transcription factors. ATAC-seq technology effectively identifies active cis-REs in a given cell type (including from single cells) by mapping accessible chromatin at base-pair resolution. However, these maps are not immediately useful for inferring specific functions of cis-REs. For this purpose, we developed a deep learning framework (CoRE-ATAC) with novel data encoders that integrate DNA sequence (reference or personal genotypes) with ATAC-seq cut sites and read pileups. CoRE-ATAC was trained on 4 cell types (n=6 samples/replicates) and accurately predicted known cis-RE functions from 7 cell types (n=40 samples) that were not used in model training (mean average precision=0.80). CoRE-ATAC enhancer predictions from 19 human islet samples coincided with genetically modulated gain/loss of enhancer activity, which was confirmed by massively parallel reporter assays (MPRAs). Finally, CoRE-ATAC effectively inferred cis-RE function from aggregate single nucleus ATAC-seq (snATAC) data from human blood-derived immune cells that overlapped with known functional annotations in sorted immune cells, which established the efficacy of these models to study cis-RE functions of rare cells without the need for cell sorting. ATAC-seq maps from primary human cells reveal individual- and cell-specific variation in cis-RE activity. CoRE-ATAC increases the functional resolution of these maps, a critical step for studying regulatory disruptions behind diseases.Author SummaryNon-coding DNA sequences serve different functional roles to regulate gene expression. For these sequences to be active, they must be accessible for proteins and other factors to bind in order to carry out a specific regulatory function. Even so, mutations within these sequences or other regulatory events may modulate their activity or regulatory function. It is therefore critical that we identify these non-coding sequences and their specific regulatory function to fully understand how specific genes are regulated. Current sequencing technologies allow us to identify accessible sequences via chromatin accessibility maps from low cell numbers, enabling the study of clinical samples. However, determining the functional role associated with these sequences remains a challenge. Towards this goal, we harnessed the power of deep learning to unravel the intricacies of chromatin accessibility maps to infer their associated gene regulatory functions. We demonstrate that our method, CoRE-ATAC, can infer regulatory functions in diverse cell types, captures activity differences modulated by genetic mutations, and can be applied to accessibility maps of single cell clusters to infer regulatory functions of rare cell populations. These inferences will further our understanding of how genes are regulated and enable the study of these mechanisms as they relate to disease.

Human cytomegalovirus US3 and UL36-38 immediate-early proteins regulate gene expression.

1992 ◽  
Vol 66 (1) ◽  
pp. 95-105 ◽  
Author(s):  
A M Colberg-Poley ◽  
L D Santomenna ◽  
P P Harlow ◽  
P A Benfield ◽  
D J Tenney
Keyword(s):  
Gene Expression ◽  
Human Cytomegalovirus ◽  
Immediate Early ◽  
Regulate Gene Expression ◽  
Early Proteins ◽  
Immediate Early Proteins ◽  
Regulate Gene

scholarly journals Arabidopsis heat shock transcription factor HSFA7b positively mediates salt stress tolerance by binding to an E-box-like motif to regulate gene expression

2019 ◽  
Vol 70 (19) ◽  
pp. 5355-5374 ◽  
Author(s):  
Dandan Zang ◽  
Jingxin Wang ◽  
Xin Zhang ◽  
Zhujun Liu ◽  
Yucheng Wang
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Heat Shock ◽  
Salt Tolerance ◽  
Stress Responses ◽  
Ion Homeostasis ◽  
Cellulose Synthase ◽  
Regulate Gene Expression ◽  
E Box ◽  
Regulate Gene

Abstract Plant heat shock transcription factors (HSFs) are involved in heat and other abiotic stress responses. However, their functions in salt tolerance are little known. In this study, we characterized the function of a HSF from Arabidopsis, AtHSFA7b, in salt tolerance. AtHSFA7b is a nuclear protein with transactivation activity. ChIP-seq combined with an RNA-seq assay indicated that AtHSFA7b preferentially binds to a novel cis-acting element, termed the E-box-like motif, to regulate gene expression; it also binds to the heat shock element motif. Under salt conditions, AtHSFA7b regulates its target genes to mediate serial physiological changes, including maintaining cellular ion homeostasis, reducing water loss rate, decreasing reactive oxygen species accumulation, and adjusting osmotic potential, which ultimately leads to improved salt tolerance. Additionally, most cellulose synthase-like (CSL) and cellulose synthase (CESA) family genes were inhibited by AtHSFA7b; some of them were randomly selected for salt tolerance characterization, and they were mainly found to negatively modulate salt tolerance. By contrast, some transcription factors (TFs) were induced by AtHSFA7b; among them, we randomly identified six TFs that positively regulate salt tolerance. Thus, AtHSFA7b serves as a transactivator that positively mediates salinity tolerance mainly through binding to the E-box-like motif to regulate gene expression.

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