scholarly journals Evolutionary dynamics of the SKN-1 → MED → END-1,3 regulatory gene cascade in Caenorhabditis endoderm specification

2019 ◽  
Author(s):  
Morris F. Maduro
Keyword(s):  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Regulatory Gene ◽  
Gata Factor ◽  
Origin And Evolution ◽  
Dna Binding Domains ◽  
Gata Factors ◽  
Binding Domains ◽  
Genes Encoding ◽  
Gene Regulatory

ABSTRACTGene regulatory networks (GRNs) with GATA factors are important in animal development, and evolution of such networks is an important problem in the field. In the nematode, Caenorhabditis elegans, the endoderm (gut) is generated from a single embryonic precursor, E. The gut is specified by an essential cascade of transcription factors in a GRN, with the maternal factor SKN-1 at the top, activating expression of the redundant med-1,2 divergent GATA factor genes, with the combination of all three contributing to activation of the paralogous end-3 and end-1 canonical GATA factor genes. In turn, these factors activate the GATA factors genes elt-2 and elt-7 to regulate intestinal fate. In this work, genome sequences from over two dozen species within the Caenorhabditis genus are used to identify putative orthologous genes encoding the MED and END-1,3 factors. The predictions are validated by comparison of gene structure, protein conservation, and putative cis-regulatory sites. The results show that all three factors occur together, but only within the Elegans supergroup of related species. While all three factors share similar DNA-binding domains, the MED factors are the most diverse as a group and exhibit unexpectedly high gene amplifications, while the END-1 orthologs are highly conserved and share additional extended regions of conservation not found in the other GATA factors. The MEME algorithm identified both known and previously unrecognized cis-regulatory motifs. The results suggest that all three genes originated at the base of the Elegans supergroup and became fixed as an essential embryonic gene regulatory network with several conserved features, although each of the three factors is under different evolutionary constraints. Based on the results, a model for the origin and evolution of the network is proposed. The set of identified MED, END-3 and END-1 factors form a robust set of factors defining an essential embryonic gene network that has been conserved for tens of millions of years, that will serve as a basis for future studies of GRN evolution.

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.

scholarly journals Divergence of gene regulatory network linkages during specification of ectoderm and mesoderm in early development of sea urchins

2016 ◽  
Author(s):  
Eric M. Erkenbrack ◽  
Eric H. Davidson
Keyword(s):  
Early Development ◽  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Sea Urchins ◽  
Regulatory Genes ◽  
Geological Time ◽  
Appreciable Change ◽  
Comparative Analyses ◽  
Temporal Gene Expression ◽  
Gene Regulatory

AbstractDevelopmental gene regulatory networks (GRNs) are assemblages of gene regulatory interactions that direct ontogeny of animal body plans. Studies of GRNs operating in early development of euechinoid sea urchins has revealed that little appreciable change has occurred since their divergence approximately 90 million years ago (mya). These observations suggest that strong conservation of GRN architecture has been maintained in early development of the sea urchin lineage. To test whether this is true for all sea urchins, comparative analyses of echinoid taxa that diverged deeper in geological time must be conducted. Recent studies highlighted extensive divergence of skeletogenic mesoderm specification in the sister clade of euechinoids, the cidaroids, suggesting that comparative analyses of cidaroid GRN architecture may confer a greater understanding of the evolutionary dynamics of developmental GRNs. Here, we report spatiotemporal patterning of 55 regulatory genes and perturbation analyses of key regulatory genes involved in euechinoid oral-aboral patterning of non-skeletogenic mesodermal and ectodermal domains in early development of the cidaroid Eucidaris tribuloides. Our results indicate that developmental GRNs directing mesodermal and ectodermal specification have undergone marked alterations since the divergence of cidaroids and euechinoids. Notably, statistical and clustering analyses of echinoid temporal gene expression datasets indicate that regulation of mesodermal genes has diverged more markedly than regulation of ectodermal genes. Although research on indirect-developing euechinoid sea urchins suggests strong conservation of GRN circuitry during early embryogenesis, this study indicates that since the divergence of cidaroids and euechinoids developmental GRNs have undergone significant divergence.

Regulation of the ANF and BNP promoters by GATA factors: Lessons learned for cardiac transcription

2001 ◽  
Vol 79 (8) ◽  
pp. 673-681 ◽  
Author(s):  
Kevin McBride ◽  
Mona Nemer
Keyword(s):  
Transcription Factors ◽  
Natriuretic Peptide ◽  
Regulatory Networks ◽  
Current Knowledge ◽  
Lessons Learned ◽  
Clinical Markers ◽  
Gata Factors ◽  
Major Mechanism ◽  
Genes Encoding ◽  
Cardiac Gene

The identification and molecular cloning of the cardiac transcription factors GATA-4, -5, and -6 has greatly contributed to our understanding of how tissue-specific transcription is achieved during cardiac growth and development. Through analysis of their interacting partners, it has also become apparent that a major mechanism underlying spatial and temporal specificity within the heart as well as in the response to cardiogenic regulators is the combinatorial interaction between cardiac-restricted and inducible transcription factors. The cardiac GATA factors appear to be fundamental contributors to these regulatory networks. Two of the first targets identified for the cardiac GATA factors were the natriuretic peptide genes encoding atrial natriuretic factor (ANF) and B-type natriuretic peptide (BNP), the major heart secretory products that are also accepted clinical markers of the diseased heart. Studies using the ANF and BNP promoters as models of cardiac-specific transcription have unraveled the pivotal role that GATA proteins play in cardiac gene expression. We review the current knowledge on the modulation of the natriuretic peptide promoters by GATA factors, including examples of combinatorial interactions between GATA proteins and diverse transcription factors.Key words: ANF, BNP, GATA factors, cardiac transcription.

scholarly journals Scalable control of developmental timetables by epigenetic switching networks

2021 ◽  
Vol 18 (180) ◽  
pp. 20210109
Author(s):  
Phuc Nguyen ◽  
Nicholas A. Pease ◽  
Hao Yuan Kueh
Keyword(s):  
Regulatory Networks ◽  
Regulatory Gene ◽  
Gene Activation ◽  
Mathematical Framework ◽  
Switching Networks ◽  
Lineage Specification ◽  
Differentiated Cells ◽  
Population Sizes ◽  
Gene Regulatory ◽  
Rate Limiting

During development, progenitor cells follow timetables for differentiation that span many cell generations. These developmental timetables are robustly encoded by the embryo, yet scalably adjustable by evolution, facilitating variation in organism size and form. Epigenetic switches, involving rate-limiting activation steps at regulatory gene loci, control gene activation timing in diverse contexts, and could profoundly impact the dynamics of gene regulatory networks controlling developmental lineage specification. Here, we develop a mathematical framework to model regulatory networks with genes controlled by epigenetic switches. Using this framework, we show that such epigenetic switching networks uphold developmental timetables that robustly span many cell generations, and enable the generation of differentiated cells in precisely defined numbers and fractions. Changes to epigenetic switching networks can readily alter the timing of developmental events within a timetable, or alter the overall speed at which timetables unfold, enabling scalable control over differentiated population sizes. With their robust, yet flexibly adjustable nature, epigenetic switching networks could represent central targets on which evolution acts to manufacture diversity in organism size and form.

EVIDENCE OF SCALE-FREE TOPOLOGY IN GENE REGULATORY NETWORK OF HUMAN TISSUES

2008 ◽  
Vol 19 (02) ◽  
pp. 283-290 ◽  
Author(s):  
M. ANDRECUT ◽  
S. A. KAUFFMAN ◽  
A. M. MADNI
Keyword(s):  
Gene Regulatory Network ◽  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Gene Network ◽  
Regulatory Networks ◽  
Regulatory Gene ◽  
Human Tissues ◽  
Scale Free ◽  
The Common ◽  
Gene Regulatory

We report the reconstruction of the topology of gene regulatory network in human tissues. The results show that the connectivity of the regulatory gene network is characterized by a scale-free distribution. This result supports the hypothesis that scale-free networks may represent the common blueprint for gene regulatory networks.

Evolution Towards Criticality in Ising Neural Agents

2020 ◽  
Vol 26 (1) ◽  
pp. 112-129 ◽  
Author(s):  
Sina Khajehabdollahi ◽  
Olaf Witkowski
Keyword(s):  
Complex Systems ◽  
Critical State ◽  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Subcritical State ◽  
Experimental Conditions ◽  
Supercritical Regime ◽  
Gene Regulatory ◽  
Human Brains ◽  
Clear Description

Criticality is thought to be crucial for complex systems to adapt at the boundary between regimes with different dynamics, where the system may transition from one phase to another. Numerous systems, from sandpiles to gene regulatory networks to swarms to human brains, seem to work towards preserving a precarious balance right at their critical point. Understanding criticality therefore seems strongly related to a broad, fundamental theory for the physics of life as it could be, which still lacks a clear description of how life can arise and maintain itself in complex systems. In order to investigate this crucial question, we model populations of Ising agents competing for resources in a simple 2D environment subject to an evolutionary algorithm. We then compare its evolutionary dynamics under different experimental conditions. We demonstrate the utility that arises at a critical state and contrast it with the behaviors and dynamics that arise far from criticality. The results show compelling evidence that not only is a critical state remarkable in its ability to adapt and find solutions to the environment, but the evolving parameters in the agents tend to flow towards criticality if starting from a supercritical regime. We present simulations showing that a system in a supercritical state will tend to self-organize towards criticality, in contrast to a subcritical state, which remains subcritical though it is still capable of adapting and increasing its fitness.

COMPLEX NETWORKS EVOLUTIONARY DYNAMICS USING GENETIC ALGORITHMS

2012 ◽  
Vol 22 (07) ◽  
pp. 1250156 ◽  
Author(s):  
DANIEL AGUILAR-HIDALGO ◽  
ANTONIO CÓRDOBA ZURITA ◽  
Ma CARMEN LEMOS FERNÁNDEZ
Keyword(s):  
Genetic Algorithm ◽  
Systems Biology ◽  
Complex Networks ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Network Dynamics ◽  
Activity Level ◽  
Transformation Rules ◽  
Gene Regulatory

Gene regulatory networks set a second order approximation to genetics understanding, where the first order is the knowledge at the single gene activity level. With the increasing number of sequenced genomes, including humans, the time has come to investigate the interactions among myriads of genes that result in complex behaviors. These characteristics are included in the novel discipline of Systems Biology. The composition and unfolding of interactions among genes determine the activity of cells and, when is considered during development, the organogenesis. Hence the interest of building representative networks of gene expression and their time evolution, i.e. the structure as the network dynamics, for certain development processes. The complexity of this kind of problems makes imperative to analyze the problem in the field of network theory and the evolutionary dynamics of complex systems.All this has led us to investigate, in a first step, the evolutionary dynamics in generic networks. Thus, the results can be used in experimental researches in the field of Systems Biology. This research aims to decode the transformation rules governing the evolutionary dynamics in a network. To do this, a genetic algorithm has been implemented in which, starting from initial and ending network states, it is possible to determine the transformation dynamics between these states by using simple acting rules. The network description is the following: (a) The network node values in the initial and ending states can be active or inactive; (b) The network links can act as activators or repressors; (c) A set of rules is established in order to transform the initial state into the ending one; (d) Due to the low connectivity, frequently observed, in gene regulatory networks, each node will hold a maximum of three inputs with no restriction on outputs. The "chromosomes" of the genetic algorithm include two parts, one related to the node links and another related to the transformation rules.The implemented rules are based on certain genetic interactions behavior. The rules and their combinations are compound by logic conditions and set the bases to the network motifs formation, which are the building blocks of the network dynamics.The implemented algorithm is able to find appropriate dynamics in complex networks evolution among different states for several cases.

scholarly journals Critical genetic program for Drosophila imaginal disc regeneration revealed by single-cell analysis

2021 ◽  
Author(s):  
Melanie I Worley ◽  
Nicholas Everetts ◽  
Riku Yasutomi ◽  
Nir Yosef ◽  
Iswar K Hariharan
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Single Cell Analysis ◽  
Specific Cell ◽  
Cell Analysis ◽  
Disc Regeneration ◽  
Discernible Effect ◽  
Genes Encoding ◽  
Wing Discs ◽  
Gene Regulatory

Whether regeneration is primarily accomplished by re-activating gene regulatory networks used previously during development or by activating novel regeneration-specific transcriptional programs remains a longstanding question. Currently, most genes implicated in regeneration also function during development. Using single-cell transcriptomics in regenerating Drosophila wing discs, we identified two regeneration-specific cell populations within the blastema. They are each composed of cells that upregulate multiple genes encoding secreted proteins that promote regeneration. In this regenerative secretory zone, the transcription factor Ets21C controls the expression of multiple regeneration-promoting genes. While eliminating Ets21C function has no discernible effect on development, it severely compromises regeneration. This Ets21C-dependent gene regulatory network is also activated in blastema-like cells in tumorous discs, suggesting that pro-regenerative mechanisms can be co-opted by tumors to promote aberrant growth.

scholarly journals Boosting heterologous protein production yield by adjusting global nitrogen and carbon metabolic regulatory networks inBacillus subtilis

2018 ◽  
Author(s):  
Haojie Cao ◽  
Julio Villatoro-Hernandez ◽  
Ruud Detert Oude Weme ◽  
Elrike Frenzel ◽  
Oscar P. Kuipers
Keyword(s):  
Bacillus Subtilis ◽  
Nutrient Intake ◽  
Regulatory Networks ◽  
Protein Production ◽  
Heterologous Protein ◽  
Heterologous Protein Production ◽  
Cell Factory ◽  
Regulatory Activity ◽  
Dna Binding Domains ◽  
Binding Domains

AbstractBacillus subtilisis extensively applied as a microorganism for the high-level production of heterologous proteins. Traditional strategies for increasing the productivity of this microbial cell factory generally focused on the targeted modification of rate-limiting components or steps. However, the longstanding problems of limited productivity of the expression host, metabolic burden and non-optimal nutrient intake, have not yet been solved to achieve production strain improvements. To tackle this problem, we systematically rewired the regulatory networks of the global nitrogen and carbon metabolism by random mutagenesis of the pleiotropic transcriptional regulators CodY and CcpA, to allow for optimal nutrient intake, translating into significantly higher heterologous protein production yields. Using a β-galactosidase expression and screening system and consecutive rounds of mutagenesis, we identified mutant variants of both CcpA and CodY that in conjunction increased production levels up to 290%. RNA-Seq and electrophoretic gel mobility shift analyses showed that amino acid substitutions within the DNA-binding domains altered the overall binding specificity and regulatory activity of the two transcription factors. Consequently, fine-tuning of the central metabolic pathways allowed for enhanced protein production levels. The improved cell factory capacity was further demonstrated by the successfully increased overexpression of GFP, xylanase and a peptidase in the double mutant strain.HighlightsThe global transcription machinery engineering (gTME) technique was applied to build mutational libraries of the pleiotropic regulators CodY and CcpA inBacillus subtilisSpecific point mutations within the DNA-binding domains of CodY and CcpA elicited alterations of the binding specificity and regulatory activityChanges in the transcriptome evoked the reprogramming of networks that gear the carbon and nitrogen metabolismThe rewired metabolic networks provided a higher building block capacity for heterologous protein production by adjusting the nutrient uptake and channeling its utilization for protein overexpression

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