scholarly journals The hardwiring of development: organization and function of genomic regulatory systems

Development ◽  
1997 ◽  
Vol 124 (10) ◽  
pp. 1851-1864 ◽  
Author(s):  
M.I. Arnone ◽  
E.H. Davidson
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Regulatory System ◽  
Development Organization ◽  
Regulatory Systems ◽  
Target Sites ◽  
Transcription Factor Target ◽  
Gene Regulatory ◽  
Genomic Regulatory Networks ◽  
And Function

The gene regulatory apparatus that directs development is encoded in the DNA, in the form of organized arrays of transcription factor target sites. Genes are regulated by interactions with multiple transcription factors and the target sites for the transcription factors required for the control of each gene constitute its cis-regulatory system. These systems are remarkably complex. Their hardwired internal organization enables them to behave as genomic information processing systems. Developmental gene regulatory networks consist of the cis-regulatory systems of all the relevant genes and the regulatory linkages amongst them. Though there is yet little explicit information, some general properties of genomic regulatory networks have become apparent. The key to understanding how genomic regulatory networks are organized, and how they work, lies in experimental analysis of cis-regulatory systems at all levels of the regulatory network.

scholarly journals Dynamical Modularity of the Genotype-Phenotype Map

2021 ◽  
Author(s):  
Johannes Jaeger ◽  
Nick Monk
Keyword(s):  
Gene Regulatory Networks ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Dynamic Behaviour ◽  
New Approach ◽  
Regulatory Systems ◽  
Alternative Approach ◽  
Gene Regulatory ◽  
And Function ◽  
Discrete Traits

An organism’s phenotype can be thought of as consisting of a set of discrete traits, able to evolve relatively independently of each other. This implies that the developmental processes generating these traits—the underlying genotype-phenotype map—must also be functionally organised in a modular manner. The genotype-phenotype map lies at the heart of evolutionary systems biology. Recently, it has become popular to define developmental modules in terms of the structure of gene regulatory networks. This approach is inherently limited: gene networks often do not have structural modularity. More generally, the connection between structure and function is quite loose. In this chapter, we discuss an alternative approach based on the concept of dynamical modularity, which overcomes many of the limitations of structural modules. A dynamical module consists of the activities of a set of genes and their interactions that generate a specific dynamic behaviour. These modules can be identified and characterised by phase-space analysis of data-driven models. We showcase the power and the promise of this new approach using several case studies. Dynamical modularity forms an important component of a general theory of the evolution of regulatory systems and the genotype-phenotype map they define.

scholarly journals Connection Between Chromosomal Location and Function of CtrA Phosphorelay Genes in Alphaproteobacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Jürgen Tomasch ◽  
Sonja Koppenhöfer ◽  
Andrew S. Lang
Keyword(s):  
Regulatory Networks ◽  
Caulobacter Crescentus ◽  
Response Regulator ◽  
Regulatory System ◽  
Physiological Processes ◽  
Gene Regulatory System ◽  
Bacterial Chromosomes ◽  
Differential Positioning ◽  
Gene Regulatory ◽  
And Function

Most bacterial chromosomes are circular, with replication starting at one origin (ori) and proceeding on both replichores toward the terminus (ter). Several studies have shown that the location of genes relative to ori and ter can have profound effects on regulatory networks and physiological processes. The CtrA phosphorelay is a gene regulatory system conserved in most alphaproteobacteria. It was first discovered in Caulobacter crescentus where it controls replication and division into a stalked and a motile cell in coordination with other factors. The locations of the ctrA gene and targets of this response regulator on the chromosome affect their expression through replication-induced DNA hemi-methylation and specific positioning along a CtrA activity gradient in the dividing cell, respectively. Here we asked to what extent the location of CtrA regulatory network genes might be conserved in the alphaproteobacteria. We determined the locations of the CtrA phosphorelay and associated genes in closed genomes with unambiguously identifiable ori from members of five alphaproteobacterial orders. The location of the phosphorelay genes was the least conserved in the Rhodospirillales followed by the Sphingomonadales. In the Rhizobiales a trend toward certain chromosomal positions could be observed. Compared to the other orders, the CtrA phosphorelay genes were conserved closer to ori in the Caulobacterales. In contrast, the genes were highly conserved closer to ter in the Rhodobacterales. Our data suggest selection pressure results in differential positioning of CtrA phosphorelay and associated genes in alphaproteobacteria, particularly in the orders Rhodobacterales, Caulobacterales and Rhizobiales that is worth deeper investigation.

scholarly journals Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets

2016 ◽  
Vol 113 (13) ◽  
pp. E1835-E1843 ◽  
Author(s):  
Mina Fazlollahi ◽  
Ivor Muroff ◽  
Eunjee Lee ◽  
Helen C. Causton ◽  
Harmen J. Bussemaker
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Nonsynonymous Mutation ◽  
Gene Regulatory ◽  
Genetic Modulators

Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae. We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.

scholarly journals Learning about Gene Regulatory Networks from Gene Deletion Experiments

2002 ◽  
Vol 3 (6) ◽  
pp. 499-503 ◽  
Author(s):  
Thomas Schlitt ◽  
Alvis Brazma
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Gene Deletion ◽  
Deletion Mutants ◽  
Major Focus ◽  
Indirect Approach ◽  
Microarray Experiments ◽  
Topological Features ◽  
Regulatory Systems ◽  
Gene Regulatory

Gene regulatory networks are a major focus of interest in molecular biology. A crucial question is how complex regulatory systems are encoded and controlled by the genome. Three recent publications have raised the question of what can be learned about gene regulatory networks from microarray experiments on gene deletion mutants. Using this indirect approach, topological features such as connectivity and modularity have been studied.

scholarly journals Epigenetic Mechanisms of Senescence in Plants

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 251
Author(s):  
Matin Miryeganeh
Keyword(s):  
Transcription Factors ◽  
Chromatin Remodeling ◽  
Regulatory Networks ◽  
Regulatory System ◽  
Epigenetic Mechanisms ◽  
Related Gene ◽  
Key Factors ◽  
Plant Senescence ◽  
Whole Plant ◽  
Age Dependent

Senescence is a major developmental transition in plants that requires a massive reprogramming of gene expression and includes various layers of regulations. Senescence is either an age-dependent or a stress-induced process, and is under the control of complex regulatory networks that interact with each other. It has been shown that besides genetic reprogramming, which is an important aspect of plant senescence, transcription factors and higher-level mechanisms, such as epigenetic and small RNA-mediated regulators, are also key factors of senescence-related genes. Epigenetic mechanisms are an important layer of this multilevel regulatory system that change the activity of transcription factors (TFs) and play an important role in modulating the expression of senescence-related gene. They include chromatin remodeling, DNA methylation, histone modification, and the RNA-mediated control of transcription factors and genes. This review provides an overview of the known epigenetic regulation of plant senescence, which has mostly been studied in the form of leaf senescence, and it also covers what has been reported about whole-plant senescence.

scholarly journals Towards a study of gene regulatory constraints to morphological evolution of the Drosophila ocellar region

2015 ◽  
Author(s):  
D. Aguilar-Hidalgo ◽  
D. Becerra-Alonso ◽  
D. García-Morales ◽  
F. Casares
Keyword(s):  
Bayesian Networks ◽  
Morphological Variation ◽  
Regulatory Networks ◽  
Morphological Evolution ◽  
Model Parameters ◽  
Regulatory Interactions ◽  
Regulatory Constraints ◽  
Gene Regulatory ◽  
Morphological Variants ◽  
And Function

ABSTRACTThe morphology and function of organs depend on coordinated changes in gene expression during development. These changes are controlled by transcription factors, signaling pathways and their regulatory interactions, which are represented by gene regulatory networks (GRNs). Therefore, the structure of an organ GRN restricts the morphological and functional variations that the organ can experience –its potential morphospace. Therefore, two important questions arise when studying any GRN: what is the predicted available morphospace and what are the regulatory linkages that contribute the most to control morphological variation within this space. Here, we explore these questions by analyzing a small “3-node” GRN model that captures the Hh-driven regulatory interactions controlling a simple visual structure: the ocellar region of Drosophila. Analysis of the model predicts that random variation of model parameters results in a specific non-random distribution of morphological variants. Study of a limited sample of Drosophilids and other dipterans finds a correspondence between the predicted phenotypic range and that found in nature. As an alternative to simulations, we apply Bayesian Networks methods in order to identify the set of parameters with the largest contribution to morphological variation. Our results predict the potential morphological space of the ocellar complex, and identify likely candidate processes to be responsible for ocellar morphological evolution using Bayesian networks. We further discuss the assumptions that the approach we have taken entails and their validity.

scholarly journals Upregulation and cell specificity of C4 genes are derived from ancestral C3 gene regulatory networks

2020 ◽  
Author(s):  
Pallavi Singh ◽  
Sean R. Stevenson ◽  
Ivan Reyna-Llorens ◽  
Gregory Reeves ◽  
Tina B. Schreier ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Transcript Accumulation ◽  
Specific Expression ◽  
Cell Specificity ◽  
Distinct Cell ◽  
Gene Regulatory

ABSTRACTThe efficient C4 pathway is based on strong up-regulation of genes found in C3 plants, but also compartmentation of their expression into distinct cell-types such as the mesophyll and bundle sheath. Transcription factors associated with these phenomena have not been identified. To address this, we undertook genome-wide analysis of transcript accumulation, chromatin accessibility and transcription factor binding in C4Gynandropsis gynandra. From these data, two models relating to the molecular evolution of C4 photosynthesis are proposed. First, increased expression of C4 genes is associated with increased binding by MYB-related transcription factors. Second, mesophyll specific expression is associated with binding of homeodomain transcription factors. Overall, we conclude that during evolution of the complex C4 trait, C4 cycle genes gain cis-elements that operate in the C3 leaf such that they become integrated into existing gene regulatory networks associated with cell specificity and photosynthesis.

scholarly journals Spatial and temporal information processing in the sea urchin embryo: modular and intramodular organization of the CyIIIa gene cis-regulatory system

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 333-348 ◽  
Author(s):  
C.V. Kirchhamer ◽  
E.H. Davidson
Keyword(s):  
Transcription Factors ◽  
Functional Organization ◽  
Specific Interaction ◽  
Regulatory Region ◽  
Regulatory System ◽  
Dna Interaction ◽  
Regulatory Function ◽  
Regulatory Structure ◽  
Spatial Expression ◽  
Target Sites

The CyIIIa cytoskeletal actin gene of Strongylocentrotus purpuratus is expressed specifically in the aboral ectoderm. In earlier work we identified a 2.3 kb cis-regulatory region that is necessary and sufficient for correct spatial and temporal expression of a CyIIIa.CAT gene. This region includes about 20 sites of specific protein-DNA interaction, at which at least nine different transcription factors may be bound. All except two of these factors have been cloned. In this work we have analyzed by deletion or mutagenesis each specific interaction. A specific function was identified for every binding site examined. These individual functions include control of amplitude and timing of expression at different phases of embryogenesis, and control of spatial expression. We show that particular negative regulatory interactions are required to repress expression of the CyIIIa.CAT construct in oral ectoderm and in skeletogenic mesenchyme at different stages. In further experiments we determined the overall functional organization of the CyIIIa cis-regulatory system, and we show that this system is modular in its regulatory structure. The ‘proximal module’ (with respect to the transcription start site) extends upstream for about 800 base pairs, and includes nine target sites serviced by six different transcription factors. Its major role is to establish CyIIIa expression in the aboral ectoderm territory as the blastomere founder cells are specified and the oral-aboral axis is determined, and to activate the CyIIIa gene late in cleavage. The ‘middle module,’ which lies upstream of the proximal module, acquires major control of CyIIIa function after the blastula stage. It includes six target sites, serviced by four different factors. The middle module is responsible for a sharp increase in expression occurring during gastrulation, mediated by the positively acting factors that bind within it. The middle module also includes sites at which two different negatively acting spatial control factors bind, the functions of which are required for correct spatial expression late in embryogenesis. The ‘distal module’ contains a number of sites at which a positively acting factor binds, but this module exercises no spatial regulatory function. Interactions within the distal module are required for the normal levels of function of both the proximal and middle modules.

scholarly journals Revealing the Key Regulators of Cell Identity in the Human Adult Pancreas

2020 ◽  
Author(s):  
Lotte Vanheer ◽  
Andrea Alex Schiavo ◽  
Matthias Van Haele ◽  
Tine Haesen ◽  
Adrian Janiszewski ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
List Type ◽  
Cell Identity ◽  
Pancreatic Cell ◽  
Human Adult ◽  
Gene Regulatory ◽  
Cellular Identity

SUMMARYCellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA sequencing datasets of the human adult pancreas, totaling 7393 cells, and comprehensively reconstruct gene regulatory networks. We show that a network of 142 transcription factors forms distinct regulatory modules that characterize pancreatic cell types. We present evidence that our approach identifies key regulators of cell identity in the human adult pancreas. We predict that HEYL and JUND are active in acinar and alpha cells, respectively, and show that these proteins are present in the human adult pancreas as well as in human induced pluripotent stem cell-derived pancreatic cells. The comprehensive gene regulatory network atlas can be explored interactively online. We anticipate our analysis to be the starting point for a more sophisticated dissection of how transcription factors regulate cell identity in the human adult pancreas. Furthermore, given that transcription factors are major regulators of embryo development and are often perturbed in diseases, a comprehensive understanding of how transcription factors work will be relevant in development and disease biology.HIGHLIGHTS-Reconstruction of gene regulatory networks for human adult pancreatic cell types-An interactive resource to explore and visualize gene expression and regulatory states-Predicting putative transcription factors driving pancreatic cell identity-HEYL and JUND as candidate regulators of acinar and alpha cell identity, respectively

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