The primary transcriptome of hormogonia from a filamentous cyanobacterium defined by cappable-seq

Hormogonia are motile filaments produced by many filamentous cyanobacteria that function in dispersal, phototaxis and the establishment of nitrogen-fixing symbioses. The gene regulatory network promoting hormogonium development is initiated by the hybrid histidine kinase HrmK, which in turn activates a sigma factor cascade consisting of SigJ, SigC and SigF. In this study, cappable-seq was employed to define the primary transcriptome of developing hormogonia in the model filamentous cyanobacterium Nostoc punctiforme ATCC 29133 in both the wild-type, and sigJ, sigC and sigF mutant strains 6 h post-hormogonium induction. A total of 1544 transcriptional start sites (TSSs) were identified that are associated with protein-coding genes and are expressed at levels likely to lead to biologically relevant transcripts in developing hormogonia. TSS expression among the sigma-factor deletion strains was highly consistent with previously reported gene expression levels from RNAseq experiments, and support the current working model for the role of these genes in hormogonium development. Analysis of SigJ-dependent TSSs corroborated the presence of the previously identified J-Box in the −10 region of SigJ-dependent promoters. Additionally, the data presented provides new insights on sequence conservation within the −10 regions of both SigC- and SigF-dependent promoters, and demonstrates that SigJ and SigC coordinate complex co-regulation not only of hormogonium-specific genes at different loci, but within an individual operon. As progress continues on defining the hormogonium gene regulatory network, this data set will serve as a valuable resource.

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Systematic Dissection of the Evolutionarily Conserved WetA Developmental Regulator across a Genus of Filamentous Fungi

mBio ◽

10.1128/mbio.01130-18 ◽

2018 ◽

Vol 9 (4) ◽

Cited By ~ 22

Author(s):

Ming-Yueh Wu ◽

Matthew E. Mead ◽

Mi-Kyung Lee ◽

Erin M. Ostrem Loss ◽

Sun-Chang Kim ◽

...

Keyword(s):

Gene Regulatory Network ◽

Filamentous Fungi ◽

Negative Feedback ◽

Regulatory Network ◽

Feedback Loop ◽

Spore Formation ◽

Negative Feedback Loop ◽

Content Type ◽

Asexual Sporulation ◽

Gene Regulatory

ABSTRACTAsexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. InAspergillus, the production of asexual spores is primarily governed by the BrlA→AbaA→WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and governs not only the morphological differentiation of spores but also the production and deposition of diverse metabolites into spores. While WetA is conserved across the genusAspergillus, the structure and degree of conservation of thewetAgene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses of comparisons betweenwetAnull mutant and wild-type asexual spores in three representative species spanning the diversity of the genusAspergillus:A. nidulans,A. flavus, andA. fumigatus. We discovered that WetA regulates asexual sporulation in all three species via a negative-feedback loop that represses BrlA, the cascade’s first step. Furthermore, data from chromatin immunoprecipitation sequencing (ChIP-seq) experiments inA. nidulansasexual spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA→AbaA→WetA cascade’s regulatory role in cellular and chemical asexual spore development is functionally conserved but that thewetA-associated GRN has diverged duringAspergillusevolution.IMPORTANCEThe formation of resilient spores is a key factor contributing to the survival and fitness of many microorganisms, including fungi. In the fungal genusAspergillus, spore formation is controlled by a complex gene regulatory network that also impacts a variety of other processes, including secondary metabolism. To gain mechanistic insights into how fungal spore formation is controlled acrossAspergillus, we dissected the gene regulatory network downstream of a major regulator of spore maturation (WetA) in three species that span the diversity of the genus: the genetic modelA. nidulans, the human pathogenA. fumigatus, and the aflatoxin producerA. flavus. Our data show that WetA regulates asexual sporulation in all three species via a negative-feedback loop and likely binds a novel regulatory element that we term the WetA response element (WRE). These results shed light on how gene regulatory networks in microorganisms control important biological processes and evolve across diverse species.

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NetExtractor: Extracting a Cerebellar Tissue Gene Regulatory Network Using Differentially Expressed High Mutual Information Binary RNA Profiles

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401067 ◽

2020 ◽

Vol 10 (9) ◽

pp. 2953-2963

Author(s):

Benafsh Husain ◽

Allison R Hickman ◽

Yuqing Hang ◽

Benjamin T Shealy ◽

Karan Sapra ◽

...

Keyword(s):

Gene Expression ◽

Mutual Information ◽

Brain Tissue ◽

Gene Regulatory Network ◽

Regulatory Network ◽

Cerebellar Hemisphere ◽

Biologically Relevant ◽

Non Linear ◽

Cerebellar Tissue ◽

Gene Regulatory

Abstract Bigenic expression relationships are conventionally defined based on metrics such as Pearson or Spearman correlation that cannot typically detect latent, non-linear dependencies or require the relationship to be monotonic. Further, the combination of intrinsic and extrinsic noise as well as embedded relationships between sample sub-populations reduces the probability of extracting biologically relevant edges during the construction of gene co-expression networks (GCNs). In this report, we address these problems via our NetExtractor algorithm. NetExtractor examines all pairwise gene expression profiles first with Gaussian mixture models (GMMs) to identify sample sub-populations followed by mutual information (MI) analysis that is capable of detecting non-linear differential bigenic expression relationships. We applied NetExtractor to brain tissue RNA profiles from the Genotype-Tissue Expression (GTEx) project to obtain a brain tissue specific gene expression relationship network centered on cerebellar and cerebellar hemisphere enriched edges. We leveraged the PsychENCODE pre-frontal cortex (PFC) gene regulatory network (GRN) to construct a cerebellar cortex (cerebellar) GRN associated with transcriptionally active regions in cerebellar tissue. Thus, we demonstrate the utility of our NetExtractor approach to detect biologically relevant and novel non-linear binary gene relationships.

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The Hybrid Histidine Kinase HrmK Is an Early-Acting Factor in the Hormogonium Gene Regulatory Network

Journal of Bacteriology ◽

10.1128/jb.00675-19 ◽

2019 ◽

Vol 202 (5) ◽

Cited By ~ 1

Author(s):

Esthefani G. Zuniga ◽

Natalie M. Figueroa ◽

Alfonso Gonzalez ◽

Adriana P. Pantoja ◽

Douglas D. Risser

Keyword(s):

Gene Regulatory Network ◽

Histidine Kinase ◽

Sigma Factor ◽

Regulatory Network ◽

Gliding Motility ◽

Model Organisms ◽

Putative Hybrid ◽

Nitrogen Fixing ◽

Gene Regulatory ◽

Hybrid Histidine Kinase

ABSTRACT Filamentous, heterocyst-forming cyanobacteria belonging to taxonomic subsections IV and V are developmentally complex multicellular organisms capable of differentiating an array of cell and filament types, including motile hormogonia. Hormogonia exhibit gliding motility that facilitates dispersal, phototaxis, and the establishment of nitrogen-fixing symbioses. The gene regulatory network (GRN) governing hormogonium development involves a hierarchical sigma factor cascade, but the factors governing the activation of this cascade are currently undefined. Here, using a forward genetic approach, we identified hrmK, a gene encoding a putative hybrid histidine kinase that functions upstream of the sigma factor cascade. The deletion of hrmK produced nonmotile filaments that failed to display hormogonium morphology or accumulate hormogonium-specific proteins or polysaccharide. Targeted transcriptional analyses using reverse transcription-quantitative PCR (RT-qPCR) demonstrated that hormogonium-specific genes both within and outside the sigma factor cascade are drastically downregulated in the absence of hrmK and that hrmK may be subject to indirect, positive autoregulation via sigJ and sigC. Orthologs of HrmK are ubiquitous among, and exclusive to, heterocyst-forming cyanobacteria. Collectively, these results indicate that hrmK functions upstream of the sigma factor cascade to initiate hormogonium development, likely by modulating the phosphorylation state of an unknown protein that may serve as the master regulator of hormogonium development in heterocyst-forming cyanobacteria. IMPORTANCE Filamentous cyanobacteria are morphologically complex, with several representative species amenable to routine genetic manipulation, making them excellent model organisms for the study of development. Furthermore, two of the developmental alternatives, nitrogen-fixing heterocysts and motile hormogonia, are essential to establish nitrogen-fixing symbioses with plant partners. These symbioses are integral to global nitrogen cycles and could be artificially recreated with crop plants to serve as biofertilizers, but to achieve this goal, detailed understanding and manipulation of the hormogonium and heterocyst gene regulatory networks may be necessary. Here, using the model organism Nostoc punctiforme, we identify a previously uncharacterized hybrid histidine kinase that is confined to heterocyst-forming cyanobacteria as the earliest known participant in hormogonium development.

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Prostate Cancer Gene Regulatory Network Inferred from RNA-Seq Data

Current Genomics ◽

10.2174/1389202919666181107122005 ◽

2019 ◽

Vol 20 (1) ◽

pp. 38-48 ◽

Cited By ~ 4

Author(s):

Daniel Moore ◽

Ricardo de Matos Simoes ◽

Matthias Dehmer ◽

Frank Emmert-Streib

Keyword(s):

Prostate Cancer ◽

Gene Regulatory Network ◽

Regulatory Network ◽

The Cancer Genome Atlas ◽

Cancer Gene ◽

Cancer Genes ◽

Rna Seq ◽

Data Set ◽

Gene Regulatory ◽

Functional Components

Background: Cancer is a complex disease with a lucid etiology and in understanding the causation, we need to appreciate this complexity. Objective: Here we are aiming to gain insights into the genetic associations of prostate cancer through a network-based systems approach using the BC3Net algorithm. Methods: Specifically, we infer a prostate cancer Gene Regulatory Network (GRN) from a large-scale gene expression data set of 333 patient RNA-seq profiles obtained from The Cancer Genome Atlas (TCGA) database. Results: We analyze the functional components of the inferred network by extracting subnetworks based on biological process information and interpret the role of known cancer genes within each process. Furthermore, we investigate the local landscape of prostate cancer genes and discuss pathological associations that may be relevant in the development of new targeted cancer therapies. Conclusion: Our network-based analysis provides a practical systems biology approach to reveal the collective gene-interactions of prostate cancer. This allows a close interpretation of biological activity in terms of the hallmarks of cancer.

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Cis-regulatory evolution integrated the Bric-à-brac transcription factors into a novel fruit fly gene regulatory network

10.1101/200360 ◽

2017 ◽

Author(s):

Maxwell J. Roeske ◽

Eric M. Camino ◽

Sumant Grover ◽

Mark Rebeiz ◽

Thomas M. Williams

Keyword(s):

Transcription Factors ◽

Gene Regulatory Network ◽

Regulatory Network ◽

Morphological Evolution ◽

Regulatory Element ◽

Fruit Fly ◽

Protein Coding ◽

Evolutionary Changes ◽

Expression Evolution ◽

Gene Regulatory

AbstractGene expression evolution through gene regulatory network (GRN) changes has gained appreciation as a driver of morphological evolution. However, understanding how GRNs evolve is hampered by finding relevant cis-regulatory element (CRE) mutations, and interpreting the protein-DNA interactions they alter. We investigated evolutionary changes in the duplicated Bric-à-brac (Bab) transcription factors and a key Bab target gene in a GRN underlying the novel dimorphic pigmentation of D. melanogaster and its relatives. It has remained uncertain how Bab was integrated within the pigmentation GRN. Here we show that Bab gained a role in sculpting sex-specific pigmentation through the evolution of binding sites in a CRE of the pigment-promoting yellow gene and without any noteworthy changes to Bab protein coding sequences. This work demonstrates how a new trait can evolve by incorporating existing transcription factors into a GRN through CRE evolution, an evolutionary path likely to predominate newly evolved functions of transcription factors.

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