scholarly journals Transcription Factors in the Fungus Aspergillus nidulans: Markers of Genetic Innovation, Network Rewiring and Conflict between Genomics and Transcriptomics

2021 ◽  
Vol 7 (8) ◽  
pp. 600
Author(s):  
Oier Etxebeste
Keyword(s):  
Transcription Factors ◽  
Aspergillus Nidulans ◽  
Growth And Development ◽  
Regulatory Networks ◽  
Regulatory Sequences ◽  
Sequence Evolution ◽  
Genomic Annotation ◽  
Associated Proteins ◽  
Duplication Events ◽  
Gain Loss

Gene regulatory networks (GRNs) are shaped by the democratic/hierarchical relationships among transcription factors (TFs) and associated proteins, together with the cis-regulatory sequences (CRSs) bound by these TFs at target promoters. GRNs control all cellular processes, including metabolism, stress response, growth and development. Due to the ability to modify morphogenetic and developmental patterns, there is the consensus view that the reorganization of GRNs is a driving force of species evolution and differentiation. GRNs are rewired through events including the duplication of TF-coding genes, their divergent sequence evolution and the gain/loss/modification of CRSs. Fungi (mainly Saccharomycotina) have served as a reference kingdom for the study of GRN evolution. Here, I studied the genes predicted to encode TFs in the fungus Aspergillus nidulans (Pezizomycotina). The analysis of the expansion of different families of TFs suggests that the duplication of TFs impacts the species level, and that the expansion in Zn2Cys6 TFs is mainly due to dispersed duplication events. Comparison of genomic annotation and transcriptomic data suggest that a significant percentage of genes should be re-annotated, while many others remain silent. Finally, a new regulator of growth and development is identified and characterized. Overall, this study establishes a novel theoretical framework in synthetic biology, as the overexpression of silent TF forms would provide additional tools to assess how GRNs are rewired.

scholarly journals Fungal Transcription factors: Markers of genetic innovation, network rewiring and conflict between genomics and transcriptomics

2021 ◽  
Author(s):  
Oier Etxebeste
Keyword(s):  
Transcription Factors ◽  
Aspergillus Nidulans ◽  
Regulatory Networks ◽  
Gene Annotation ◽  
Regulatory Sequences ◽  
Sequence Evolution ◽  
Transcriptomic Data ◽  
Associated Proteins ◽  
Duplication Events ◽  
Gain Loss

AbstractGene Regulatory Networks (GRNs) are shaped by the democratic/hierarchical relationships among transcription factors (TFs) and associated proteins, together with the cis-regulatory sequences (CRSs) bound by these TFs at target promoters. GRNs control all cellular processes, including metabolism, stress-response, growth and development. Due to the ability to modify morphogenetic and developmental patterns, there is the consensus view that the reorganization of GRNs is a driving force of species evolution and differentiation. Duplication of genes coding for TFs, their divergent sequence evolution and gain/loss/modification of CRSs are events causing GRN rewiring. Fungi (mainly Saccharomycotina) have served as a reference kingdom for the study of GRN evolution. Here, I studied the genes predictably coding for TFs in the fungus Aspergillus nidulans (Pezizomycotina). Bioinformatics results support the view that duplication events of TF-coding genes potentially impact the species levels. Discrepancy between gene-annotation and transcriptomic data suggests that duplication of genes potentially coding for TFs are not always accompanied by the generation of functional forms and modification of regulatory potential. Overall, this study establishes a novel theoretical framework in synthetic biology, since overexpression of silent or primarily non-functional TF forms would provide additional tools for assessment of the mechanisms triggering GRN rewiring.One-sentence summaryAn in silico study of the predicted set of transcriptional regulators in the fungus Aspergillus nidulans, their conservation patterns and the correlation between gene annotations and transcriptomic data

scholarly journals The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers inEnterobacteriaceae

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
W. Ryan Will ◽  
Peter Brzovic ◽  
Isolde Le Trong ◽  
Ronald E. Stenkamp ◽  
Matthew B. Lawrenz ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Regulatory Networks ◽  
Antimicrobial Agents ◽  
Efflux Pumps ◽  
Evolutionary Divergence ◽  
Regulatory Sequences ◽  
Emerging Pathogens ◽  
Practical Applications

ABSTRACTGene duplication and subsequent evolutionary divergence have allowed conserved proteins to develop unique roles. The MarR family of transcription factors (TFs) has undergone extensive duplication and diversification in bacteria, where they act as environmentally responsive repressors of genes encoding efflux pumps that confer resistance to xenobiotics, including many antimicrobial agents. We have performed structural, functional, and genetic analyses of representative members of the SlyA/RovA lineage of MarR TFs, which retain some ancestral functions, including repression of their own expression and that of divergently transcribed multidrug efflux pumps, as well as allosteric inhibition by aromatic carboxylate compounds. However, SlyA and RovA have acquired the ability to countersilence horizontally acquired genes, which has greatly facilitated the evolution ofEnterobacteriaceaeby horizontal gene transfer. SlyA/RovA TFs in different species have independently evolved novel regulatory circuits to provide the enhanced levels of expression required for their new role. Moreover, in contrast to MarR, SlyA is not responsive to copper. These observations demonstrate the ability of TFs to acquire new functions as a result of evolutionary divergence of bothcis-regulatory sequences and intransinteractions with modulatory ligands.IMPORTANCEBacteria primarily evolve via horizontal gene transfer, acquiring new traits such as virulence and antibiotic resistance in single transfer events. However, newly acquired genes must be integrated into existing regulatory networks to allow appropriate expression in new hosts. This is accommodated in part by the opposing mechanisms of xenogeneic silencing and countersilencing. An understanding of these mechanisms is necessary to understand the relationship between gene regulation and bacterial evolution. Here we examine the functional evolution of an important lineage of countersilencers belonging to the ancient MarR family of classical transcriptional repressors. We show that although members of the SlyA lineage retain some ancestral features associated with the MarR family, theircis-regulatory sequences have evolved significantly to support their new function. Understanding the mechanistic requirements for countersilencing is critical to understanding the pathoadaptation of emerging pathogens and also has practical applications in synthetic biology.

scholarly journals Deciphering the rules underlying xenogeneic silencing and counter-silencing of Lsr2-like proteins

2019 ◽  
Author(s):  
Johanna Wiechert ◽  
Andrei Filipchyk ◽  
Max Hünnefeld ◽  
Cornelia Gätgens ◽  
Ralf Heermann ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Corynebacterium Glutamicum ◽  
Regulatory Networks ◽  
Gene Clusters ◽  
Nucleation Site ◽  
Toggle Switch ◽  
Genetic Traits ◽  
Associated Proteins ◽  
Genomic Regions

ABSTRACTLsr2-like nucleoid-associated proteins play an important role as xenogeneic silencers (XS) of horizontally acquired genomic regions in actinobacteria. In this study, we systematically analyzed the in vivo constraints underlying silencing and counter-silencing of the Lsr2-like protein CgpS in Corynebacterium glutamicum. Genome-wide analysis revealed binding of CgpS to regions featuring a distinct drop in GC-profile close to the transcription start site (TSS), but also identified an overrepresented motif with multiple A/T steps at the nucleation site of the nucleoprotein complex. Binding of specific transcription factors (TFs) may oppose XS activity leading to counter-silencing. Following a synthetic counter-silencing approach, target gene activation was realized by inserting operator sites of an effector-responsive TF within various CgpS target promoters resulting in an increased promoter activity upon TF binding. Analysis of reporter constructs revealed maximal counter-silencing when the TF operator site was inserted at the position of maximal CgpS coverage. This principle was implemented in a synthetic toggle switch, which features a robust and reversible response to effector availability highlighting the potential for biotechnological applications. Altogether, our results provide comprehensive insights into how Lsr2 silencing and counter-silencing shapes evolutionary network expansion in this medically- and biotechnologically-relevant bacterial phylum.IMPORTANCEIn actinobacteria, Lsr2-like nucleoid-associated proteins function as xenogeneic silencers (XS) of horizontally acquired genomic regions, including viral elements, virulence gene clusters in Mycobacterium tuberculosis, and genes involved in cryptic specialized metabolism in Streptomyces species. Consequently, a detailed mechanistic understanding of Lsr2 binding in vivo is relevant as a potential drug target and for the identification novel bioactive compounds. Here, we followed an in vivo approach to investigate the rules underlying xenogeneic silencing and counter-silencing of the Lsr2-like XS CgpS from Corynebacterium glutamicum. Our results demonstrated that CgpS distinguishes between self and foreign by recognizing a distinct drop in GC-profile in combination with a short, sequence specific motif at the nucleation site. Following a synthetic counter-silencer approach, we studied the potential and constraints of transcription factors to counteract CgpS silencing thereby facilitating the integration of new genetic traits into host regulatory networks.

scholarly journals The role of transposable elements in the ecological morphogenesis under the influence of stress

2019 ◽  
Vol 23 (4) ◽  
pp. 380-389 ◽  
Author(s):  
R. N. Mustafin ◽  
E. K. Khusnutdinova
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Insertional Mutagenesis ◽  
Specific Protein ◽  
Regulatory Sequences ◽  
Rapid Variability ◽  
Protein Coding ◽  
Genome Variability ◽  
Protein Coding Genes ◽  
Non Coding Rna

In natural selection, insertional mutagenesis is an important source of genome variability. Transposons are sensors of environmental stress effects, which contribute to adaptation and speciation. These effects are due to changes in the mechanisms of morphogenesis, since transposons contain regulatory sequences that have cis and trans effects on specific protein-coding genes. In variability of genomes, the horizontal transfer of transposons plays an important role, because it contributes to changing the composition of transposons and the acquisition of new properties. Transposons are capable of site-specific transpositions, which lead to the activation of stress response genes. Transposons are sources of non-coding RNA, transcription factors binding sites and protein-coding genes due to domestication, exonization, and duplication. These genes contain nucleotide sequences that interact with non-coding RNAs processed from transposons transcripts, and therefore they are under the control of epigenetic regulatory networks involving transposons. Therefore, inherited features of the location and composition of transposons, along with a change in the phenotype, play an important role in the characteristics of responding to a variety of environmental stressors. This is the basis for the selection and survival of organisms with a specific composition and arrangement of transposons that contribute to adaptation under certain environmental conditions. In evolution, the capability to transpose into specific genome sites, regulate gene expression, and interact with transcription factors, along with the ability to respond to stressors, is the basis for rapid variability and speciation by altering the regulation of ontogenesis. The review presents evidence of tissue-specific and stage-specific features of transposon activation and their role in the regulation of cell differentiation to confirm their role in ecological morphogenesis.

The Repertoire of DNA-Binding Transcription Factors in Prokaryotes: Functional and Evolutionary Lessons

2012 ◽  
Vol 95 (3) ◽  
pp. 315-329 ◽  
Author(s):  
Ernesto Perez-Rueda ◽  
Mario Alberto Martinez-Nuñez
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Regulatory Networks ◽  
Environmental Changes ◽  
Regulate Gene Expression ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Comprehensive Picture ◽  
Duplication Events

The capabilities of organisms to contend with environmental changes depend on their genes and their ability to regulate their expression. DNA-binding transcription factors (TFs) play a central role in this process, because they regulate gene expression positively and/or negatively, depending on the operator context and ligand-binding status. In this review, we summarise recent findings regarding the function and evolution of TFs in prokaryotes. We consider the abundance of TFs in bacteria and archaea, the role of DNA-binding domains and their partner domains, and the effects of duplication events in the evolution of regulatory networks. Finally, a comprehensive picture for how regulatory networks have evolved in prokaryotes is provided.

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 HbxB Is a Key Regulator for Stress Response and β-Glucan Biogenesis in Aspergillus nidulans

2021 ◽  
Vol 9 (1) ◽  
pp. 144
Author(s):  
Sung-Hun Son ◽  
Mi-Kyung Lee ◽  
Ye-Eun Son ◽  
Hee-Soo Park
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Aspergillus Nidulans ◽  
Deletion Mutant ◽  
Phenotypic Analysis ◽  
Spore Viability ◽  
Fungal Development ◽  
Expression Of Genes ◽  
Trehalose Biosynthesis

Homeobox transcription factors are conserved in eukaryotes and act as multi-functional transcription factors in filamentous fungi. Previously, it was demonstrated that HbxB governs fungal development and spore viability in Aspergillus nidulans. Here, the role of HbxB in A. nidulans was further characterized. RNA-sequencing revealed that HbxB affects the transcriptomic levels of genes associated with trehalose biosynthesis and response to thermal, oxidative, and radiation stresses in asexual spores called conidia. A phenotypic analysis found that hbxB deletion mutant conidia were more sensitive to ultraviolet stress. The loss of hbxB increased the mRNA expression of genes associated with β-glucan degradation and decreased the amount of β-glucan in conidia. In addition, hbxB deletion affected the expression of the sterigmatocystin gene cluster and the amount of sterigmatocystin. Overall, these results indicated that HbxB is a key transcription factor regulating trehalose biosynthesis, stress tolerance, β-glucan degradation, and sterigmatocystin production in A.nidulans conidia.

scholarly journals Comprehensive network modeling from single cell RNA sequencing of human and mouse reveals well conserved transcription regulation of hematopoiesis

BMC Genomics ◽  
2020 ◽  
Vol 21 (S11) ◽  
Author(s):  
Shouguo Gao ◽  
Zhijie Wu ◽  
Xingmin Feng ◽  
Sachiko Kajigaya ◽  
Xujing Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factors ◽  
Single Cell ◽  
Rna Sequencing ◽  
Transcription Regulation ◽  
Regulatory Networks ◽  
Stem Cell Differentiation ◽  
Hematopoietic Stem ◽  
Single Cell Rna Sequencing ◽  
Human And Mouse

Abstract Background Presently, there is no comprehensive analysis of the transcription regulation network in hematopoiesis. Comparison of networks arising from gene co-expression across species can facilitate an understanding of the conservation of functional gene modules in hematopoiesis. Results We used single-cell RNA sequencing to profile bone marrow from human and mouse, and inferred transcription regulatory networks in each species in order to characterize transcriptional programs governing hematopoietic stem cell differentiation. We designed an algorithm for network reconstruction to conduct comparative transcriptomic analysis of hematopoietic gene co-expression and transcription regulation in human and mouse bone marrow cells. Co-expression network connectivity of hematopoiesis-related genes was found to be well conserved between mouse and human. The co-expression network showed “small-world” and “scale-free” architecture. The gene regulatory network formed a hierarchical structure, and hematopoiesis transcription factors localized to the hierarchy’s middle level. Conclusions Transcriptional regulatory networks are well conserved between human and mouse. The hierarchical organization of transcription factors may provide insights into hematopoietic cell lineage commitment, and to signal processing, cell survival and disease initiation.

scholarly journals Comparative transcriptome analysis reveals key genes associated with pigmentation in radish (Raphanus sativus L.) skin and flesh

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jifang Zhang ◽  
Jian Zhao ◽  
Qunyun Tan ◽  
Xiaojun Qiu ◽  
Shiyong Mei
Keyword(s):  
Transcription Factors ◽  
Raphanus Sativus ◽  
Regulatory Networks ◽  
Anthocyanin Biosynthesis ◽  
Comparative Transcriptome ◽  
Structural Genes ◽  
Key Genes ◽  
Transcript Profiles ◽  
Species Specific ◽  
Anthocyanin Biosynthetic Genes

AbstractRadish (Raphanus sativus) is an important vegetable worldwide that exhibits different flesh and skin colors. The anthocyanins responsible for the red and purple coloring in radishes possess nutritional value and pharmaceutical potential. To explore the structural and regulatory networks related to anthocyanin biosynthesis and identify key genes, we performed comparative transcriptome analyses of the skin and flesh of six colored radish accessions. The transcript profiles showed that each accession had a species-specific transcript profile. For radish pigmentation accumulation, the expression levels of anthocyanin biosynthetic genes (RsTT4, RsC4H, RsTT7, RsCCOAMT, RsDFR, and RsLDOX) were significantly upregulated in the red- and purple-colored accessions, but were downregulated or absent in the white and black accessions. The correlation test, combined with metabolome (PCC > 0.95), revealed five structural genes (RsTT4, RsDFR, RsCCOAMT, RsF3H, and RsBG8L) and three transcription factors (RsTT8-1, RsTT8-2, and RsPAR1) to be significantly correlated with flavonoids in the skin of the taproot. Four structural genes (RsBG8L, RsDFR, RsCCOAMT, and RsLDOX) and nine transcription factors (RsTT8-1, RsTT8-2, RsMYB24L, RsbHLH57, RsPAR2L, RsbHLH113L, RsOGR3L, RsMYB24, and RsMYB34L) were found to be significantly correlated with metabolites in the flesh of the taproot. This study provides a foundation for future studies on the gene functions and genetic diversity of radish pigmentation and should aid in the cultivation of new valuable radish varieties.

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