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Systems biology study of transcriptional and post-transcriptional co-regulatory network sheds light on key regulators involved in important biological processes in Citrus sinensis.

ABSTRACT: Transcriptional and post-transcriptional regulators including transcription regulator, transcription factor and miRNA are the main endogenous molecular elements which control complex cellular mechanisms such as development, growth and response to biotic and abiotic stresses in a coordinated manner in plants. Utilizing the most recent information on such relationships in a plant species, obtained from high-throughput experimental technologies and advanced computational tools, we can reconstruct its co-regulatory network which consequently sheds light on key regulators involved in its important biological processes. In this article, combined systems biology approaches such as mining the literatures, various databases and network reconstruction, analysis, and visualization tools were employed to infer and visualize the coregulatory relationships between miRNAs and transcriptional regulators in Citrus sinensis. Using computationally and experimentally verified miRNA-target interactions and constructed co-expression networks on array-based data, 10 coregulatory networks and 10 corresponding subgraphs include FFL motifs were obtained for 10 distinct tissues/conditions. Then PPI subnetworks were extracted for transcripts/genes included in mentioned subgraphs in order to the functional analysis of extracted coregulatory circuits. These proposed coregulatory connections shed light on precisely identifying C. sinensis metabolic pathways key switches, which are demanded for ultimate goals such as genome editing.

SUBMITTER: Khodadadi E

PROVIDER: S-EPMC5391350 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Systems biology study of transcriptional and post-transcriptional co-regulatory network sheds light on key regulators involved in important biological processes in <i>Citrus sinensis</i>.

Khodadadi Ehsan E Mehrabi Ali Ashraf AA Najafi Ali A Rastad Saber S Masoudi-Nejad Ali A

Physiology and molecular biology of plants : an international journal of functional plant biology 20170210 2

Transcriptional and post-transcriptional regulators including transcription regulator, transcription factor and miRNA are the main endogenous molecular elements which control complex cellular mechanisms such as development, growth and response to biotic and abiotic stresses in a coordinated manner in plants. Utilizing the most recent information on such relationships in a plant species, obtained from high-throughput experimental technologies and advanced computational tools, we can reconstruct i ...[more]

PMID: 28461722

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Project description:Endoplasmic reticulum (ER) stress is characterized by the accumulation of misfolded proteins due to an impairment of ER quality control pathways leading to the activation of a defense system, called unfolded protein response (UPR). While thyrocytes are supposed to be highly susceptible to environmental conditions that cause ER stress due to the synthesis of large amounts of secretory proteins required for thyroid hormone synthesis, systematic investigations on the effect of ER stress on expression of key genes of thyroid hormone synthesis and their transcriptional regulators are lacking. Since the aim of the ER stress-induced UPR is to restore ER homeostasis and to facilitate cell survival through transient shutdown of ribosomal protein translation, we hypothesized that the expression of genes involved in thyroid hormone synthesis and their transcriptional regulators, all of which are not essential for cell survival, are down-regulated in thyrocytes during ER stress, while sterol regulatory element-binding proteins (SREBPs) are activated during ER stress in thyrocytes. Treatment of FRTL-5 thyrocytes with the ER stress inducer tunicamycin (TM) dose-dependently increased the mRNA and/or protein levels of known UPR target genes, stimulated phosphorylation of the ER stress sensor protein kinase RNA-like ER kinase (PERK) and of the PERK target protein eukaryotic initiation factor 2α (eIF2α) and caused splicing of the ER stress-sensitive transcription factor X-box binding protein (XBP-1) (P < 0.05). The mRNA levels and/or protein levels of genes involved in thyroid hormone synthesis, sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), their transcriptional regulators and thyrotropin (TSH) receptor and the uptake of Na125I were reduced at the highest concentration of TM tested (0.1 μg/mL; P < 0.05). Proteolytic activation of the SREBP-1c pathway was not observed in FRTL-5 cells treated with TM, whereas TM reduced proteolytic activation of the SREBP-2 pathway at 0.1 μg TM/mL (P < 0.05). In conclusion, the expression of key genes involved in thyroid hormone synthesis and their critical regulators and of the TSH receptor as well as the uptake of iodide is attenuated in thyrocytes during mild ER stress. Down-regulation of NIS, TPO and TG during ER stress is likely the consequence of impaired TSH/TSHR signaling in concert with reduced expression of critical transcriptional regulators of these genes.

Project description:The human commensal and opportunistic fungal pathogen Candida albicans displays extensive genetic and phenotypic variation across clinical isolates. Here, we performed RNA sequencing on 21 well-characterized isolates to examine how genetic variation contributes to gene expression differences and to link these differences to phenotypic traits. C. albicans adapts primarily through clonal evolution, and yet hierarchical clustering of gene expression profiles in this set of isolates did not reproduce their phylogenetic relationship. Strikingly, strain-specific gene expression was prevalent in some strain backgrounds. Association of gene expression with phenotypic data by differential analysis, linear correlation, and assembly of gene networks connected both previously characterized and novel genes with 23 C. albicans traits. Construction of de novo gene modules produced a gene atlas incorporating 67% of C. albicans genes and revealed correlations between expression modules and important phenotypes such as systemic virulence. Furthermore, targeted investigation of two modules that have novel roles in growth and filamentation supported our bioinformatic predictions. Together, these studies reveal widespread transcriptional variation across C. albicans isolates and identify genetic and epigenetic links to phenotypic variation based on coexpression network analysis.IMPORTANCE Infectious fungal species are often treated uniformly despite clear evidence of genotypic and phenotypic heterogeneity being widespread across strains. Identifying the genetic basis for this phenotypic diversity is extremely challenging because of the tens or hundreds of thousands of variants that may distinguish two strains. Here, we use transcriptional profiling to determine differences in gene expression that can be linked to phenotypic variation among a set of 21 Candida albicans isolates. Analysis of this transcriptional data set uncovered clear trends in gene expression characteristics for this species and new genes and pathways that were associated with variation in pathogenic processes. Direct investigation confirmed functional predictions for a number of new regulators associated with growth and filamentation, demonstrating the utility of these approaches in linking genes to important phenotypes.

Dataset Information

Systems biology study of transcriptional and post-transcriptional co-regulatory network sheds light on key regulators involved in important biological processes in Citrus sinensis.

Publications

Systems biology study of transcriptional and post-transcriptional co-regulatory network sheds light on key regulators involved in important biological processes in <i>Citrus sinensis</i>.

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