scholarly journals Regulatory network structure determines patterns of intermolecular epistasis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Mato Lagator ◽  
Srdjan Sarikas ◽  
Hande Acar ◽  
Jonathan P Bollback ◽  
Călin C Guet
Keyword(s):  
Transcription Factor ◽  
Adaptive Evolution ◽  
Network Structure ◽  
Phenotypic Variation ◽  
Regulatory Network ◽  
Individual Component ◽  
Regulatory System ◽  
Molecular Systems ◽  
Transcriptional Regulatory ◽  
Dna Binding Site

Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution.

scholarly journals CoryneRegNet 2: An Integrative Bioinformatics Approach for Reconstruction and Comparison of Transcriptional Regulatory Networks in Prokaryotes

2006 ◽  
Vol 3 (2) ◽  
pp. 1-13 ◽  
Author(s):  
Jan Baumbach ◽  
Karina Brinkrolf ◽  
Tobias Wittkop ◽  
Andreas Tauch ◽  
Sven Rahmann
Keyword(s):  
Transcription Factor ◽  
Data Warehouse ◽  
Binding Sites ◽  
Regulatory Network ◽  
High Performance ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Search Tool ◽  
Gene Regulatory

SummaryCoryneRegNet is an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. Initially, it was designed to provide methods for the analysis and visualization of the gene regulatory network of Corynebacterium glutamicum. Now we integrated the genomes and transcriptional interactions of three other corynebacteria, C. diphtheriae, C. efficiens, and C. jeikeium into CoryneRegNet; providing comparative analysis and visualization with GraphVis. We also integrated the high-performance PSSM search tool PoSSuM search to detect potential transcription factor binding sites within and across species. As an application, we reconstruct in silico the regulatory network of the iron metabolism regulator DtxR in the four corynebacteria.CoryneRegNet is freely accessible at https://www.cebitec.uni-bielefeld.de/groups/gi/software/coryneregnet/. The final slash (/) is mandatory. In order to use the GraphVis feature, Java (at least version 1.4.2) is required.

scholarly journals Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion

mSystems ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
David Bergenholm ◽  
Guodong Liu ◽  
Petter Holland ◽  
Jens Nielsen
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Chromatin Immunoprecipitation ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Network ◽  
Lambda Exonuclease ◽  
Transcriptional Regulatory ◽  
Exonuclease Digestion

ABSTRACT To build transcription regulatory networks, transcription factor binding must be analyzed in cells grown under different conditions because their responses and targets differ depending on environmental conditions. We performed whole-genome analysis of the DNA binding of five Saccharomyces cerevisiae transcription factors involved in lipid metabolism, Ino2, Ino4, Hap1, Oaf1, and Pip2, in response to four different environmental conditions in chemostat cultures, which allowed us to keep the specific growth rate constant. Chromatin immunoprecipitation with lambda exonuclease digestion (ChIP-exo) enabled the detection of binding events at a high resolution. We discovered a large number of unidentified targets and thus expanded functions for each transcription factor (e.g., glutamate biosynthesis as a target of Oaf1 and Pip2). Moreover, condition-dependent binding of transcription factors in response to cell metabolic state (e.g., differential binding of Ino2 between fermentative and respiratory metabolic conditions) was clearly suggested. Combining the new binding data with previously published data from transcription factor deletion studies revealed the high complexity of the transcriptional regulatory network for lipid metabolism in yeast, which involves the combinatorial and complementary regulation by multiple transcription factors. We anticipate that our work will provide insights into transcription factor binding dynamics that will prove useful for the understanding of transcription regulatory networks. IMPORTANCE Transcription factors play a crucial role in the regulation of gene expression and adaptation to different environments. To better understand the underlying roles of these adaptations, we performed experiments that give us high-resolution binding of transcription factors to their targets. We investigated five transcription factors involved in lipid metabolism in yeast, and we discovered multiple novel targets and condition-specific responses that allow us to draw a better regulatory map of the lipid metabolism.

scholarly journals Genome-Wide Mapping of Binding Sites Reveals Multiple Biological Functions of the Transcription Factor Cst6p in Saccharomyces cerevisiae

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Guodong Liu ◽  
David Bergenholm ◽  
Jens Nielsen
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Regulatory Network ◽  
Deletion Mutant ◽  
Transcriptional Regulatory Network ◽  
Biological Processes ◽  
Genome Wide ◽  
Transcriptional Regulatory

ABSTRACT In the model eukaryote Saccharomyces cerevisiae , the transcription factor Cst6p has been reported to play important roles in several biological processes. However, the genome-wide targets of Cst6p and its physiological functions remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. Cst6p binds to the promoter regions of 59 genes with various biological functions when cells are grown on ethanol but hardly binds to the promoter at any gene when cells are grown on glucose. The retarded growth of the CST6 deletion mutant on ethanol is attributed to the markedly decreased expression of NCE103 , encoding a carbonic anhydrase, which is a direct target of Cst6p. The target genes of Cst6p have a large overlap with those of stress-responsive transcription factors, such as Sko1p and Skn7p. In addition, a CST6 deletion mutant growing on ethanol shows hypersensitivity to oxidative stress and ethanol stress, assigning Cst6p as a new member of the stress-responsive transcriptional regulatory network. These results show that mapping of genome-wide binding sites can provide new insights into the function of transcription factors and highlight the highly connected and condition-dependent nature of the transcriptional regulatory network in S. cerevisiae . IMPORTANCE Transcription factors regulate the activity of various biological processes through binding to specific DNA sequences. Therefore, the determination of binding positions is important for the understanding of the regulatory effects of transcription factors. In the model eukaryote Saccharomyces cerevisiae , the transcription factor Cst6p has been reported to regulate several biological processes, while its genome-wide targets remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. We show that the binding of Cst6p to its target promoters is condition dependent and explain the mechanism for the retarded growth of the CST6 deletion mutant on ethanol. Furthermore, we demonstrate that Cst6p is a new member of a stress-responsive transcriptional regulatory network. These results provide deeper understanding of the function of the dynamic transcriptional regulatory network in S. cerevisiae .

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