scholarly journals Construction and application of a co-expression network in Mycobacterium tuberculosis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Jiang ◽  
Xian Sun ◽  
Wei Wu ◽  
Li Li ◽  
Hai Wu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Transcription Factors ◽  
Correlation Coefficients ◽  
Hypoxic Condition ◽  
Expression Levels ◽  
Transcriptional Regulatory ◽  
Validation Experiment ◽  
Gene Correlation ◽  
Transcriptional Regulatory Mechanisms ◽  
Different Response

Abstract Because of its high pathogenicity and infectivity, tuberculosis is a serious threat to human health. Some information about the functions of the genes in Mycobacterium tuberculosis genome was currently available, but it was not enough to explore transcriptional regulatory mechanisms. Here, we applied the WGCNA (Weighted Gene Correlation Network Analysis) algorithm to mine pooled microarray datasets for the M. tuberculosis H37Rv strain. We constructed a co-expression network that was subdivided into 78 co-expression gene modules. The different response to two kinds of vitro models (a constant 0.2% oxygen hypoxia model and a Wayne model) were explained based on these modules. We identified potential transcription factors based on high Pearson’s correlation coefficients between the modules and genes. Three modules that may be associated with hypoxic stimulation were identified, and their potential transcription factors were predicted. In the validation experiment, we determined the expression levels of genes in the modules under hypoxic condition and under overexpression of potential transcription factors (Rv0081, furA (Rv1909c), Rv0324, Rv3334, and Rv3833). The experimental results showed that the three identified modules related to hypoxia and that the overexpression of transcription factors could significantly change the expression levels of genes in the corresponding modules.

scholarly journals CarD and RbpA modify the kinetics of initial transcription and slow promoter escape of the Mycobacterium tuberculosis RNA polymerase

2019 ◽  
Vol 47 (13) ◽  
pp. 6685-6698 ◽  
Author(s):  
Drake Jensen ◽  
Ana Ruiz Manzano ◽  
Jayan Rammohan ◽  
Christina L Stallings ◽  
Eric A Galburt
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Complex Formation ◽  
Rna Polymerase ◽  
Transcription Initiation ◽  
Promoter Escape ◽  
Rate Limiting Step ◽  
Nucleotide Incorporation ◽  
Transcriptional Regulatory ◽  
Open Complex Formation ◽  
Transcriptional Regulatory Mechanisms

Abstract The pathogen Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, enacts unique transcriptional regulatory mechanisms when subjected to host-derived stresses. Initiation of transcription by the Mycobacterial RNA polymerase (RNAP) has previously been shown to exhibit different open complex kinetics and stabilities relative to Escherichia coli (Eco) RNAP. However, transcription initiation rates also depend on the kinetics following open complex formation such as initial nucleotide incorporation and subsequent promoter escape. Here, using a real-time fluorescence assay, we present the first in-depth kinetic analysis of initial transcription and promoter escape for the Mtb RNAP. We show that in relation to Eco RNAP, Mtb displays slower initial nucleotide incorporation but faster overall promoter escape kinetics on the Mtb rrnAP3 promoter. Furthermore, in the context of the essential transcription factors CarD and RbpA, Mtb promoter escape is slowed via differential effects on initially transcribing complexes. Finally, based on their ability to increase the rate of open complex formation and decrease the rate of promoter escape, we suggest that CarD and RbpA are capable of activation or repression depending on the rate-limiting step of a given promoter's basal initiation kinetics.

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.

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 Mutations of folC cause increased susceptibility to sulfamethoxazole in Mycobacterium tuberculosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ruiqi Wang ◽  
Kun Li ◽  
Jifang Yu ◽  
Jiaoyu Deng ◽  
Yaokai Chen
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type Strain ◽  
Wild Type Strain ◽  
Clinical Isolates ◽  
Aminobenzoic Acid ◽  
Wild Type ◽  
Dihydropteroate Synthase ◽  
Expression Levels ◽  
Encoding Gene ◽  
Increased Susceptibility

AbstractPrevious studies showed that mutation of folC caused decreased expression of the dihydropteroate synthase encoding gene folP2 in Mycobacterium tuberculosis (M. tuberculosis). We speculated that mutation of folC in M. tuberculosis might affect the susceptibility to sulfamethoxazole (SMX). To prove this, 53 clinical isolates with folC mutations were selected and two folC mutants (I43A, I43T) were constructed based on M. tuberculosis H37Ra. The results showed that 42 of the 53 clinical isolates (79.2%) and the two lab-constructed folC mutants were more sensitive to SMX. To probe the mechanism by which folC mutations make M. tuberculosis more sensitive to SMX, folP2 was deleted in H37Ra, and expression levels of folP2 were compared between H37Ra and the two folC mutants. Although deletion of folP2 resulted in increased susceptibility to SMX, no difference in folP2 expression was observed. Furthermore, production levels of para-aminobenzoic acid (pABA) were compared between the folC mutants and the wild-type strain, and results showed that folC mutation resulted in decreased production of pABA. Taken together, we show that folC mutation leads to decreased production of pABA in M. tuberculosis and thus affects its susceptibility to SMX, which broadens our understanding of mechanisms of susceptibilities to antifolates in this bacterium.

scholarly journals Development and Carcinogenesis: Roles of GATA Factors in the Sympathoadrenal and Urogenital Systems

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 299
Author(s):  
Takashi Moriguchi
Keyword(s):  
Transcription Factors ◽  
Developmental Process ◽  
Current Knowledge ◽  
Gynecologic Cancers ◽  
Inherited Diseases ◽  
Gata Factors ◽  
Transcriptional Regulatory ◽  
Gata Family

The GATA family of transcription factors consists of six proteins (GATA1-6) that control a variety of physiological and pathological processes. In particular, GATA2 and GATA3 are coexpressed in a number of tissues, including in the urogenital and sympathoadrenal systems, in which both factors participate in the developmental process and tissue maintenance. Furthermore, accumulating studies have demonstrated that GATA2 and GATA3 are involved in distinct types of inherited diseases as well as carcinogenesis in diverse tissues. This review summarizes our current knowledge of how GATA2 and GATA3 participate in the transcriptional regulatory circuitry during the development of the sympathoadrenal and urogenital systems, and how their dysregulation results in the carcinogenesis of neuroblastoma, renal urothelial, and gynecologic cancers.

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 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

Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium pannonicum

Planta Medica ◽  
2018 ◽  
Vol 84 (11) ◽  
pp. 786-794
Author(s):  
Weiyun Chai ◽  
Lu Chen ◽  
Xiao-Yuan Lian ◽  
Zhizhen Zhang
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Cell Cycle Regulators ◽  
Expression Levels ◽  
Multiple Tumor ◽  
Glioma Growth

AbstractTripolinolate A as a new bioactive phenolic ester was previously isolated from a halophyte of Tripolium pannonicum. However, the in vitro and in vivo anti-glioma effects and mechanism of tripolinolate A have not been investigated. This study has demonstrated that (1) tripolinolate A inhibited the proliferation of different glioma cells with IC50 values of 7.97 to 14.02 µM and had a significant inhibitory effect on the glioma growth in U87MG xenograft nude mice, (2) tripolinolate A induced apoptosis in glioma cells by downregulating the expressions of antiapoptotic proteins and arrested glioma cell cycle at the G2/M phase by reducing the expression levels of cell cycle regulators, and (3) tripolinolate A also remarkably reduced the expression levels of several glioma metabolic enzymes and transcription factors. All data together suggested that tripolinolate A had significant in vitro and in vivo anti-glioma effects and the regulation of multiple tumor-related regulators and transcription factors might be responsible for the activities of tripolinolate A against glioma.

scholarly journals Screening Driving Transcription Factors in the Processing of Gastric Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Guangzhong Xu ◽  
Kai Li ◽  
Nengwei Zhang ◽  
Bin Zhu ◽  
Guosheng Feng
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Regulatory Mechanisms ◽  
Integrated Analysis ◽  
Transcriptional Regulatory

Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer.Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed.Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer.Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis.

scholarly journals Dissecting the Repertoire of DNA-Binding Transcription Factors of the Archaeon Pyrococcus furiosus DSM 3638

Life ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 40 ◽  
Author(s):  
Antonia Denis ◽  
Mario Alberto Martínez-Núñez ◽  
Silvia Tenorio-Salgado ◽  
Ernesto Perez-Rueda
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Regulatory Networks ◽  
Pyrococcus Furiosus ◽  
Structural Domain ◽  
Transcriptional Regulatory Networks ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Transcriptional Regulatory ◽  
Cellular Domain

In recent years, there has been a large increase in the amount of experimental evidence for diverse archaeal organisms, and these findings allow for a comprehensive analysis of archaeal genetic organization. However, studies about regulatory mechanisms in this cellular domain are still limited. In this context, we identified a repertoire of 86 DNA-binding transcription factors (TFs) in the archaeon Pyrococcus furiosus DSM 3638, that are clustered into 32 evolutionary families. In structural terms, 45% of these proteins are composed of one structural domain, 41% have two domains, and 14% have three structural domains. The most abundant DNA-binding domain corresponds to the winged helix-turn-helix domain; with few alternative DNA-binding domains. We also identified seven regulons, which represent 13.5% (279 genes) of the total genes in this archaeon. These analyses increase our knowledge about gene regulation in P. furiosus DSM 3638 and provide additional clues for comprehensive modeling of transcriptional regulatory networks in the Archaea cellular domain.

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