scholarly journals Intricate genetic programs controlling dormancy in Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Abrar A. Abidi ◽  
Eliza J. R. Peterson ◽  
Mario L. Arrieta-Ortiz ◽  
Boris Aguilar ◽  
James T. Yurkovich ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Time Course ◽  
Experimental System ◽  
Topology Analysis ◽  
Transcriptional Dynamics ◽  
Regulatory Circuits ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Location Map ◽  
Favorable Conditions

AbstractMycobacterium tuberculosis (MTB), responsible for the deadliest infectious disease worldwide, displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and opportunistically exploit immunocompromised individuals. Uncovering the gene regulatory programs that underlie the dramatic phenotypic shifts in MTB during disease latency and reactivation has posed an extraordinary challenge. We developed a novel experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the chain of transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding location map and insights from network topology analysis, we identified regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions.One Sentence SummaryHigh-resolution transcriptional time-course reveals six-state genetic program that enables MTB to enter and exit hypoxia-induced dormancy.

scholarly journals Expansion of the circadian transcriptome in Brassica rapa and genome-wide diversification of paralog expression patterns

2020 ◽  
Author(s):  
Kathleen Greenham ◽  
Ryan C. Sartor ◽  
Stevan Zorich ◽  
Ping Lou ◽  
Todd C. Mockler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brassica Rapa ◽  
Regulatory Network ◽  
Time Course ◽  
Expression Patterns ◽  
Time Of Day ◽  
Circadian Regulation ◽  
Genome Wide ◽  
Circadian Control ◽  
Gene Regulatory

AbstractAn important challenge of crop improvement strategies is assigning function to paralogs in polyploid crops. Gene expression is one method for determining the activity of paralogs; however, the majority of transcript abundance data represents a static point that does not consider the spatial and temporal dynamics of the transcriptome. Studies in Arabidopsis have estimated up to 90% of the transcriptome to be under diel or circadian control depending on the condition. As a result, time of day effects on the transcriptome have major implications on how we characterize gene activity. In this study, we aimed to resolve the circadian transcriptome in the polyploid crop Brassica rapa and explore the fate of multicopy orthologs of Arabidopsis circadian regulated genes. We performed a high-resolution time course study with 2 h sampling density to capture the genes under circadian control. Strikingly, more than two-thirds of expressed genes exhibited rhythmicity indicative of circadian regulation. To compare the expression patterns of paralogous genes, we developed a program in R called DiPALM (Differential Pattern Analysis by Linear Models) that analyzes time course data to identify transcripts with significant pattern differences. Using DiPALM, we identified genome-wide divergence of expression patterns among retained paralogs. Cross-comparison with a previously generated diel drought experiment in B. rapa revealed evidence for differential drought response for these diverging paralog pairs. Using gene regulatory network models we compared transcription factor targets between B. rapa and Arabidopsis circadian networks to reveal additional evidence for divergence in expression between B. rapa paralogs that may be driven in part by variation in conserved non coding sequences. These findings provide new insight into the rapid expansion and divergence of the transcriptional network in a polyploid crop and offer a new method for assessing paralog activity at the transcript level.SignificanceThe circadian regulation of the transcriptome leads to time of day changes in gene expression that coordinates environmental conditions with physiological responses. Brassica rapa, a morphologically diverse crop species, has undergone whole genome triplication since diverging from Arabidopsis resulting in an expansion of gene copy number. To examine how this expansion has influenced the circadian transcriptome we developed a new method for comparing gene expression patterns. This method facilitated the discovery of genome-wide expansion of expression patterns for genes present in multiple copies and divergence in temporal abiotic stress response. We find support for conserved sequences outside the gene body contributing to these expression pattern differences and ultimately generating new connections in the gene regulatory network.

scholarly journals SPLICE-q: a Python tool for genome-wide quantification of splicing efficiency

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Verônica R. de Melo Costa ◽  
Julianus Pfeuffer ◽  
Annita Louloupi ◽  
Ulf A. V. Ørom ◽  
Rosario M. Piro
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Time Course ◽  
Progressive Increase ◽  
Rna Seq ◽  
Transcript Processing ◽  
Aberrant Transcript ◽  
Genome Wide ◽  
Splicing Efficiency ◽  
Nascent Rna

Abstract Background Introns are generally removed from primary transcripts to form mature RNA molecules in a post-transcriptional process called splicing. An efficient splicing of primary transcripts is an essential step in gene expression and its misregulation is related to numerous human diseases. Thus, to better understand the dynamics of this process and the perturbations that might be caused by aberrant transcript processing it is important to quantify splicing efficiency. Results Here, we introduce SPLICE-q, a fast and user-friendly Python tool for genome-wide SPLICing Efficiency quantification. It supports studies focusing on the implications of splicing efficiency in transcript processing dynamics. SPLICE-q uses aligned reads from strand-specific RNA-seq to quantify splicing efficiency for each intron individually and allows the user to select different levels of restrictiveness concerning the introns’ overlap with other genomic elements such as exons of other genes. We applied SPLICE-q to globally assess the dynamics of intron excision in yeast and human nascent RNA-seq. We also show its application using total RNA-seq from a patient-matched prostate cancer sample. Conclusions Our analyses illustrate that SPLICE-q is suitable to detect a progressive increase of splicing efficiency throughout a time course of nascent RNA-seq and it might be useful when it comes to understanding cancer progression beyond mere gene expression levels. SPLICE-q is available at: https://github.com/vrmelo/SPLICE-q

scholarly journals Prediction of genome-wide effects of single nucleotide variants on transcription factor binding

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sebastian Carrasco Pro ◽  
Katia Bulekova ◽  
Brian Gregor ◽  
Adam Labadorf ◽  
Juan Ignacio Fuxman Bass
Keyword(s):  
Binding Sites ◽  
Cancer Type ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
The Impact ◽  
The Relationship

Abstract Single nucleotide variants (SNVs) located in transcriptional regulatory regions can result in gene expression changes that lead to adaptive or detrimental phenotypic outcomes. Here, we predict gain or loss of binding sites for 741 transcription factors (TFs) across the human genome. We calculated ‘gainability’ and ‘disruptability’ scores for each TF that represent the likelihood of binding sites being created or disrupted, respectively. We found that functional cis-eQTL SNVs are more likely to alter TF binding sites than rare SNVs in the human population. In addition, we show that cancer somatic mutations have different effects on TF binding sites from different TF families on a cancer-type basis. Finally, we discuss the relationship between these results and cancer mutational signatures. Altogether, we provide a blueprint to study the impact of SNVs derived from genetic variation or disease association on TF binding to gene regulatory regions.

scholarly journals Pluripotency Transcription Factor Oct4 Mediates Stepwise Nucleosome Demethylation and Depletion

2015 ◽  
Vol 35 (6) ◽  
pp. 1014-1025 ◽  
Author(s):  
Arvind Shakya ◽  
Catherine Callister ◽  
Alon Goren ◽  
Nir Yosef ◽  
Neha Garg ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Chromatin Immunoprecipitation ◽  
Time Course ◽  
Embryonic Stem ◽  
Assay System ◽  
Histone Demethylation ◽  
Oct4 Expression ◽  
Genome Wide ◽  
Histone Lysine Demethylase ◽  
Lysine Demethylase

The mechanisms whereby the crucial pluripotency transcription factor Oct4 regulates target gene expression are incompletely understood. Using an assay system based on partially differentiated embryonic stem cells, we show that Oct4 opposes the accumulation of local H3K9me2 and subsequent Dnmt3a-mediated DNA methylation. Upon binding DNA, Oct4 recruits the histone lysine demethylase Jmjd1c. Chromatin immunoprecipitation (ChIP) time course experiments identify a stepwise Oct4 mechanism involving Jmjd1c recruitment and H3K9me2 demethylation, transient FACT ( fa cilitates c hromatin t ransactions) complex recruitment, and nucleosome depletion. Genome-wide and targeted ChIP confirms binding of newly synthesized Oct4, together with Jmjd1c and FACT, to the Pou5f1 enhancer and a small number of other Oct4 targets, including the Nanog promoter. Histone demethylation is required for both FACT recruitment and H3 depletion. Jmjd1c is required to induce endogenous Oct4 expression and fully reprogram fibroblasts to pluripotency, indicating that the assay system identifies functional Oct4 cofactors. These findings indicate that Oct4 sequentially recruits activities that catalyze histone demethylation and depletion.

scholarly journals Temporal transcriptomic profiling reveals dynamic changes in gene expression of Xenopus animal cap upon activin treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumeko Satou-Kobayashi ◽  
Jun-Dal Kim ◽  
Akiyoshi Fukamizu ◽  
Makoto Asashima
Keyword(s):  
Time Course ◽  
Transforming Growth Factor ◽  
Transcriptome Profiling ◽  
Transforming Growth Factor Β ◽  
Activin A ◽  
Cytokine Signaling ◽  
Molecular Characteristics ◽  
Transcriptional Dynamics

AbstractActivin, a member of the transforming growth factor-β (TGF-β) superfamily of proteins, induces various tissues from the amphibian presumptive ectoderm, called animal cap explants (ACs) in vitro. However, it remains unclear how and to what extent the resulting cells recapitulate in vivo development. To comprehensively understand whether the molecular dynamics during activin-induced ACs differentiation reflect the normal development, we performed time-course transcriptome profiling of Xenopus ACs treated with 50 ng/mL of activin A, which predominantly induced dorsal mesoderm. The number of differentially expressed genes (DEGs) in response to activin A increased over time, and totally 9857 upregulated and 6663 downregulated DEGs were detected. 1861 common upregulated DEGs among all Post_activin samples included several Spemann’s organizer genes. In addition, the temporal transcriptomes were clearly classified into four distinct groups in correspondence with specific features, reflecting stepwise differentiation into mesoderm derivatives, and a decline in the regulation of nuclear envelop and golgi. From the set of early responsive genes, we also identified the suppressor of cytokine signaling 3 (socs3) as a novel activin A-inducible gene. Our transcriptome data provide a framework to elucidate the transcriptional dynamics of activin-driven AC differentiation, reflecting the molecular characteristics of early normal embryogenesis.

Perception and first defense responses against Pseudomonas syringae pv. phaseolicola in Phaseolus vulgaris L.: identification of Wall-Associated Kinase receptors

2021 ◽  
Author(s):  
Alfonso Gonzalo De la Rubia ◽  
María Luz Centeno ◽  
Victor Moreno-González ◽  
María De Castro ◽  
Penélope García-Angulo
Keyword(s):  
Phaseolus Vulgaris ◽  
Pseudomonas Syringae ◽  
Time Course ◽  
Early Time ◽  
Experimental System ◽  
Antioxidant Response ◽  
Defense Responses ◽  
Cellular Damage ◽  
Initial Increase ◽  
Phaseolus Vulgaris L

Common bean (Phaseolus vulgaris L.) is attacked by several pathogens such as the biotrophic gamma-proteobacterium Pseudomonas syringae pv. phaseolicola (Pph). In order to study the Pph-bean interaction during the first stages of infection, leaf disks of a susceptible bean variety named Riñón were infected with a pathogenic Pph. Using this experimental system, six new putative Wall-Associated Kinase (WAKs) receptors, previously identified in silico, were tested. These six bean WAKs (PvWAKs) showed high protein sequence homology to the well-described Arabidopsis WAK1 (AtWAK1) receptor and, by phylogenetic analysis, clustered together with AtWAKs. The expression of PvWAK1 increased at very early stages after the Pph infection. Time course experiments were performed to evaluate the accumulation of apoplastic H2O2, Ca2+ influx, total H2O2, antioxidant enzymatic activities, lipid peroxidation, and the concentrations of abscisic acid (ABA) and salicylic acid (SA), as well as the expression of six defense-related genes – MEKK-1, MAPKK, WRKY33, RIN4, PR1 and NPR1. The results showed that overexpression of PR1 occurred 2 h after Pph infection without a concomitant increase in SA levels. Although apoplastic H2O2 increased after infection, the oxidative burst was neither intense nor rapid and an efficient antioxidant response did not occur, suggesting that the observed cellular damage was due to the initial increase in total H2O2 at early time points after infection. In conclusion, the Riñón variety can perceive the presence of Pph, but this recognition only results in a modest and slow activation of host defenses, leading to high susceptibility to Pph.

Abstract MP208: A Shared Fog2 / Tbx5-dependent Gene Regulatory Network Identified By Transcription Factor-dependent Non-coding RNA Profiling Modulates Cardiac Rhythm

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Linsin A Smith ◽  
Carlos Perez-Cervantes ◽  
Michael Broman ◽  
Rangarajan Nadadur ◽  
Jeff Steimle ◽  
...  
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Cardiac Rhythm ◽  
Association Studies ◽  
Genome Wide Association ◽  
Calcium Handling ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Atrial Rhythm

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting over 33 million individuals throughout the world. AF is highly heritable and recent genome-wide association studies (GWAS) have cumulatively identified over 100 loci associated with AF risk. Genome-wide association studies (GWAS) often identify transcription factor (TF) loci in association with complex human diseases, implying that a significant transcriptional component underlies human disease risk and etiology. The transcription factors ZFPM2 (FOG2), GATA4, and TBX5 have all been implicated in human AF risk by genetic studies. We hypothesized that FOG2, GATA4, and TBX5 functionally interact to regulate a gene regulatory network essential for atrial rhythm control. We generated a novel mouse model of spontaneous AF based on FOG2 overexpression. FOG2 ChIP-seq identified FOG2 genomic localization at loci co-occupied by GATA4, a known FOG2 binding partner. However, we found that FOG2 OE caused gene expression alterations that correlated more highly with TBX5-dependent rather than GATA4-dependent gene expression, including a module of calcium handling genes required for atrial rhythm homeostasis. We applied TF-dependent non-coding transcriptional profiling to examine the FOG2 dependent atrial GRN, which identified 805 candidate regulatory regions with accessible chromatin and FOG2 dependent ncRNAs. TBX5 removal and FOG2 OE caused highly correlated dysregulation of ncRNA expression at open chromatin regions genome-wide, suggesting a functional interaction between TBX5 and FOG2. Furthermore, FOG2 OE only affected enhancer activity by altered ncRNA abundance at locations of TBX5 co-binding. The shared TBX5/FOG2 genomic interaction predicted a potential genetic interaction, and we found that cardiac rhythm abnormalities caused by Tbx5 haploinsufficiency were rescued by Fog2 haploinsufficiency. Taken together, TF-dependent ncRNA-profiling revealed an interconnected cardiac rhythm gene regulatory network (GRN) between FOG2, TBX5 and GATA4. These data nominate a specific model in which FOG2 is recruited by GATA4 to modulate a co-bound TBX5-dependent atrial gene regulatory network for calcium handling and atrial rhythm homeostasis.

scholarly journals Inference of gene regulatory networks from genome-wide knockout fitness data

2012 ◽  
Vol 29 (3) ◽  
pp. 338-346 ◽  
Author(s):  
L. Wang ◽  
X. Wang ◽  
A. P. Arkin ◽  
M. S. Samoilov
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Genome Wide ◽  
Gene Regulatory
Sign in / Sign up

Export Citation Format

Share Document