scholarly journals Evolution of transcriptional control of antigenic variation and virulence in human and ape malaria parasites

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mackensie R. Gross ◽  
Rosie Hsu ◽  
Kirk W. Deitsch
Keyword(s):  
Gene Family ◽  
Transcriptional Control ◽  
Antigenic Variation ◽  
Expression Profiles ◽  
Transmission Dynamics ◽  
Immune Recognition ◽  
Chronic Infections ◽  
Remarkable Change ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms

Abstract Background The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. This unicellular organism is a member of a subgenus of Plasmodium called the Laverania that infects apes, with P. falciparum being the only member that infects humans. The exceptional virulence of this species to humans can be largely attributed to a family of variant surface antigens placed by the parasites onto the surface of infected red blood cells that mediate adherence to the vascular endothelium. These proteins are encoded by a large, multicopy gene family called var, with each var gene encoding a different form of the protein. By changing which var gene is expressed, parasites avoid immune recognition, a process called antigenic variation that underlies the chronic nature of malaria infections. Results Here we show that the common ancestor of the branch of the Laverania lineage that includes the human parasite underwent a remarkable change in the organization and structure of elements linked to the complex transcriptional regulation displayed by the var gene family. Unlike the other members of the Laverania, the clade that gave rise to P. falciparum evolved distinct subsets of var genes distinguishable by different upstream transcriptional regulatory regions that have been associated with different expression profiles and virulence properties. In addition, two uniquely conserved var genes that have been proposed to play a role in coordinating transcriptional switching similarly arose uniquely within this clade. We hypothesize that these changes originated at a time of dramatic climatic change on the African continent that is predicted to have led to significant changes in transmission dynamics, thus selecting for patterns of antigenic variation that enabled lengthier, more chronic infections. Conclusions These observations suggest that changes in transmission dynamics selected for significant alterations in the transcriptional regulatory mechanisms that mediate antigenic variation in the parasite lineage that includes P. falciparum. These changes likely underlie the chronic nature of these infections as well as their exceptional virulence.

scholarly journals Post-transcriptional mechanisms distinguish human and chimp forebrain progenitor cells

2019 ◽  
Author(s):  
Daniela A Grassi ◽  
Per Ludvik Brattås ◽  
Jeovanis G Valdés ◽  
Melinda Rezeli ◽  
Marie E Jönsson ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Transcriptional Control ◽  
Neural Progenitor Cells ◽  
Specific Expression ◽  
Control Of Gene Expression ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
High Level ◽  
Rna Levels

AbstractThe forebrain has expanded in size and complexity during hominoid evolution. The contribution of post-transcriptional control of gene expression to this process is unclear. Using in-depth proteomics in combination with bulk and single-cell RNA sequencing, we analyzed protein and RNA levels of almost 5,000 genes in human and chimpanzee forebrain neural progenitor cells. We found that species differences in protein expression level was often independent of RNA levels, and more frequent than transcriptomic differences. Low-abundant proteins were more likely to show species-specific expression levels, while proteins expressed at a high level appeared to have evolved under stricter constraints. Our study implicates a previously unappreciated broad and important role for post-transcriptional regulatory mechanisms in the evolution of the human forebrain.

scholarly journals Transcription factor co-binding patterns drive conserved regulatory outcomes

2017 ◽  
Author(s):  
Adam G. Diehl ◽  
Alan P. Boyle
Keyword(s):  
Transcription Factor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Control ◽  
Regulatory Sequence ◽  
Transcriptional Regulatory ◽  
Genetic Mechanisms ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
Human And Mouse

ABSTRACTThe mouse has been widely used as a model system in which to study human genetic mechanisms. However, part of the difficulty in translating findings from mouse is that, despite high levels of gene conservation, regulatory control networks between human and mouse have been extensively rewired. To understand common themes of regulatory control we look beyond physical sharing of regulatory sequence, where extensive turnover of individual transcription factor binding sites complicates cross-species prediction of specific functions, and instead look at conserved properties of the regulatory code itself. We define regulatory conservation in terms of a grammar with shared, species-specific, and tissue-specific segments, and show that this grammar is more predictive of shared chromatin states and gene expression profiles than shared occupancy alone. Furthermore, we demonstrate a marked enrichment of disease associated variation in conserved grammatical patterns. These findings offer new understanding of transcriptional regulatory mechanisms shared between human and mouse.

scholarly journals Genome-wide identification, classification and expression analysis of the JmjC domain-containing histone demethylase gene family in Jatropha curcas L.

2021 ◽  
Author(s):  
Jie Wang ◽  
Xiaoke Jiang ◽  
Hanrui Bai ◽  
Changning Liu
Keyword(s):  
Gene Family ◽  
Jatropha Curcas ◽  
Transcriptional Regulatory Network ◽  
Expression Profiles ◽  
Regulatory Element ◽  
Target Prediction ◽  
Regulatory Elements ◽  
Element Analysis ◽  
Transcriptional Regulatory ◽  
Jmjc Domain

Abstract JmjC domain-containing proteins, an important family of histone lysine demethylase, play significant roles in maintaining the homeostasis of histone methylation. In this study, we comprehensively analyzed the JmjC domain-containing gene family in Jatropha curcas and found 20 JmjC domain-containing genes (JcJMJ genes). Phylogenetic analysis revealed that these JcJMJ genes can be classified into five major subgroups, and genes in each subgroup had similar motif and domain composition. Cis-regulatory element analysis showed that the number and types of cis-regulatory elements owned by the promoter of JcJMJ genes in different subgroups were significantly different. Moreover, the miRNA target prediction result revealed a complicated miRNA-mediated post-transcriptional regulatory network, in which JcJMJ genes were regulated by different numbers and types of miRNAs. Further analysis of the tissue and stress expression profiles showed that many JcJMJ genes had tissue and stress expression specificity. All these results provided valuable information for understanding the evolution of JcJMJ genes and the complex transcriptional and post-transcriptional regulation involved and laid the foundation for further functional analysis of JcJMJ genes.

Genome-wide identification and analysis of the GATA transcription factor gene family in Ustilaginoidea virens

Genome ◽  
2019 ◽  
Vol 62 (12) ◽  
pp. 807-816 ◽  
Author(s):  
Mina Yu ◽  
Junjie Yu ◽  
Huijuan Cao ◽  
Mingli Yong ◽  
Yongfeng Liu
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Ustilaginoidea Virens ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Starting Point ◽  
Reactive Oxygen Species Stress ◽  
False Smut ◽  
Transcriptional Regulatory Mechanisms

In filamentous fungi, the conserved transcription factors play important roles in multiple cellular and developmental processes. The GATA proteins, a family of GATA-binding zinc finger transcription factors, play diverse functions in fungi. Ustilaginoidea virens is an economically important pathogen-causing rice false smut worldwide. To gain additional insight into the cellular and molecular mechanisms of this pathogen, in this study, we identified and functionally characterized seven GATA proteins from the U. virens genome (UvGATA). Sequences analysis indicated that these GATA proteins are divided into seven clades. The proteins in each clade contained conserved clade-specific sequences and structures, thus leading to the same motif serving different purposes in various contexts. The expression profiles of UvGATA genes at different infection stages and under H2O2 stress were detected. Results showed that the majority of UvGATA genes performed functions at both processes, thereby confirming the roles of these genes in pathogenicity and reactive oxygen species stress tolerance. This study provided an important starting point to further explore the biological functions of UvGATA genes and increased our understanding of their potential transcriptional regulatory mechanisms in U. virens.

scholarly journals Insight into the bZIP Gene Family in Solanum tuberosum: Genome and Transcriptome Analysis to Understand the Roles of Gene Diversification in Spatiotemporal Gene Expression and Function

2020 ◽  
Vol 22 (1) ◽  
pp. 253
Author(s):  
Venura Herath ◽  
Jeanmarie Verchot
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Functional Groups ◽  
Leucine Zipper ◽  
Expression Profiles ◽  
Crop Improvement ◽  
Potato Virus X ◽  
Tissue Growth ◽  
Abiotic Stress Response ◽  
Sequence Alignments

The basic region-leucine zipper (bZIP) transcription factors (TFs) form homodimers and heterodimers via the coil–coil region. The bZIP dimerization network influences gene expression across plant development and in response to a range of environmental stresses. The recent release of the most comprehensive potato reference genome was used to identify 80 StbZIP genes and to characterize their gene structure, phylogenetic relationships, and gene expression profiles. The StbZIP genes have undergone 22 segmental and one tandem duplication events. Ka/Ks analysis suggested that most duplications experienced purifying selection. Amino acid sequence alignments and phylogenetic comparisons made with the Arabidopsis bZIP family were used to assign the StbZIP genes to functional groups based on the Arabidopsis orthologs. The patterns of introns and exons were conserved within the assigned functional groups which are supportive of the phylogeny and evidence of a common progenitor. Inspection of the leucine repeat heptads within the bZIP domains identified a pattern of attractive pairs favoring homodimerization, and repulsive pairs favoring heterodimerization. These patterns of attractive and repulsive heptads were similar within each functional group for Arabidopsis and S. tuberosum orthologs. High-throughput RNA-seq data indicated the most highly expressed and repressed genes that might play significant roles in tissue growth and development, abiotic stress response, and response to pathogens including Potato virus X. These data provide useful information for further functional analysis of the StbZIP gene family and their potential applications in crop improvement.

Transcriptional Control of Parturition: Insights from Gene Regulation Studies in the Myometrium

2021 ◽  
Author(s):  
Nawrah Khader ◽  
Virlana M Shchuka ◽  
Oksana Shynlova ◽  
Jennifer A Mitchell
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Progesterone Receptors ◽  
Activator Protein 1 ◽  
Transcriptional Regulatory Networks ◽  
Regulatory Pathways ◽  
Transcriptional Regulatory ◽  
Mechanistic Basis ◽  
Labour Onset

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.

scholarly journals The nuclear receptor HNF4 drives a brush border gene program conserved across murine intestine, kidney, and embryonic yolk sac

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Chen ◽  
Shirley Luo ◽  
Abigail Dupre ◽  
Roshan P. Vasoya ◽  
Aditya Parthasarathy ◽  
...  
Keyword(s):  
Brush Border ◽  
Regulatory Networks ◽  
Critical Role ◽  
Yolk Sac ◽  
Apical Surface ◽  
Transcriptional Regulatory Networks ◽  
Chromatin Looping ◽  
Multiple Organs ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms

AbstractThe brush border is comprised of microvilli surface protrusions on the apical surface of epithelia. This specialized structure greatly increases absorptive surface area and plays crucial roles in human health. However, transcriptional regulatory networks controlling brush border genes are not fully understood. Here, we identify that hepatocyte nuclear factor 4 (HNF4) transcription factor is a conserved and important regulator of brush border gene program in multiple organs, such as intestine, kidney and yolk sac. Compromised brush border gene signatures and impaired transport were observed in these tissues upon HNF4 loss. By ChIP-seq, we find HNF4 binds and activates brush border genes in the intestine and kidney. H3K4me3 HiChIP-seq identifies that HNF4 loss results in impaired chromatin looping between enhancers and promoters at gene loci of brush border genes, and instead enhanced chromatin looping at gene loci of stress fiber genes in the intestine. This study provides comprehensive transcriptional regulatory mechanisms and a functional demonstration of a critical role for HNF4 in brush border gene regulation across multiple murine epithelial tissues.

scholarly journals Genome-Wide Analysis and Characterization of the Aux/IAA Family Genes Related to Floral Scent Formation in Hedychium coronarium

2019 ◽  
Vol 20 (13) ◽  
pp. 3235 ◽  
Author(s):  
Yanguo Ke ◽  
Farhat Abbas ◽  
Yiwei Zhou ◽  
Rangcai Yu ◽  
Yuechong Yue ◽  
...  
Keyword(s):  
Gene Family ◽  
Developmental Stages ◽  
Floral Scent ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Virus Induced Gene Silencing ◽  
Cut Flowers ◽  
Flower Opening ◽  
Hedychium Coronarium

Auxin plays a key role in different plant growth and development processes, including flower opening and development. The perception and signaling of auxin depend on the cooperative action of various components, among which auxin/indole-3-acetic acid (Aux/IAA) proteins play an imperative role. In a recent study, the entire Aux/IAA gene family was identified and comprehensively analyzed in Hedychium coronarium, a scented species used as an ornamental plant for cut flowers. Phylogenetic analysis showed that the Aux/IAA gene family in H. coronarium is slightly contracted compared to Arabidopsis, with low levels of non-canonical proteins. Sequence analysis of promoters showed numerous cis-regulatory elements related to various phytohormones. HcIAA genes showed distinct expression patterns in different tissues and flower developmental stages, and some HcIAA genes showed significant responses to auxin and ethylene, indicating that Aux/IAAs may play an important role in linking hormone signaling pathways. Based on the expression profiles, HcIAA2, HcIAA4, HcIAA6 and HcIAA12, were selected as candidate genes and HcIAA2 and HcIAA4 were screened for further characterization. Downregulation of HcIAA2 and HcIAA4 by virus-induced gene silencing in H. coronarium flowers modified the total volatile compound content, suggesting that HcIAA2 and HcIAA4 play important roles in H. coronarium floral scent formation. The results presented here will provide insights into the putative roles of HcIAA genes and will assist the elucidation of their precise roles during floral scent formation.

scholarly journals Genetics and Epigenetics of Atrial Fibrillation

2020 ◽  
Vol 21 (16) ◽  
pp. 5717 ◽  
Author(s):  
Estefanía Lozano-Velasco ◽  
Diego Franco ◽  
Amelia Aranega ◽  
Houria Daimi
Keyword(s):  
Atrial Fibrillation ◽  
Regulatory Networks ◽  
Association Studies ◽  
Functional Characterization ◽  
The Elderly ◽  
Supraventricular Arrhythmia ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms

Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence exponentially increases with age and could reach up to 8% in the elderly population. The management of AF is a complex issue that is addressed by extensive ongoing basic and clinical research. AF centers around different types of disturbances, including ion channel dysfunction, Ca2+-handling abnormalities, and structural remodeling. Genome-wide association studies (GWAS) have uncovered over 100 genetic loci associated with AF. Most of these loci point to ion channels, distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Recently, the discovery of post-transcriptional regulatory mechanisms, involving non-coding RNAs (especially microRNAs), DNA methylation, and histone modification, has allowed to decipher how a normal heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. This review aims to provide a current state of the field regarding the identification and functional characterization of AF-related epigenetic regulatory networks

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