scholarly journals Feed-forward regulation adaptively evolves via dynamics rather than topology when there is intrinsic noise

2018 ◽  
Author(s):  
Kun Xiong ◽  
Alex K. Lancaster ◽  
Mark L. Siegal ◽  
Joanna Masel
Keyword(s):  
Regulatory Networks ◽  
Null Model ◽  
Intrinsic Noise ◽  
Slow Pathway ◽  
Transcriptional Regulatory Networks ◽  
Spurious Signal ◽  
Feed Forward ◽  
Transcriptional Regulatory ◽  
Canonical Motif ◽  
External Signals

AbstractWe develop a null model of the evolution of transcriptional regulatory networks, and use it to support an adaptive origin for a canonical “motif”, a 3-node feed-forward loop (FFL) hypothesized to filter out short spurious signals by integrating information from a fast and a slow pathway. Our mutational model captures the intrinsically high prevalence of weak affinity transcription factor binding sites. We also capture stochasticity and delays in gene expression that distort external signals and intrinsically generate noise. Functional FFLs evolve readily under selection for the hypothesized function, but not in negative controls. Interestingly, a 4-node “diamond” motif also emerged as a short spurious signal filter. The diamond uses expression dynamics rather than path length to provide fast and slow pathways. When there is no external spurious signal to filter out, but only internally generated noise, only the diamond and not the FFL evolves.

scholarly journals Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks

2017 ◽  
Vol 112 (8) ◽  
pp. 1539-1550 ◽  
Author(s):  
Michael A. Rowland ◽  
Ahmed Abdelzaher ◽  
Preetam Ghosh ◽  
Michael L. Mayo
Keyword(s):  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Feed Forward ◽  
Transcriptional Regulatory

scholarly journals Network design principle for robust oscillatory behaviors with respect to biological noise

2021 ◽  
Author(s):  
Lingxia Qiao ◽  
Zhi-Bo Zhang ◽  
Wei Zhao ◽  
Ping Wei ◽  
Lei Zhang
Keyword(s):  
Chemical Reactions ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Network ◽  
Intrinsic Noise ◽  
Biological Noise ◽  
Extrinsic Noise ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Activator Inhibitor ◽  
Oscillatory Behaviors

Oscillatory behaviors, which are ubiquitous in transcriptional regulatory networks, are often subject to inevitable biological noise. Thus a natural question is how transcriptional regulatory networks can robustly achieve accurate oscillation in the presence of biological noise. Here, we search all two- and three-node transcriptional regulatory network topologies for those robustly capable of accurate oscillation against the parameter variability (extrinsic noise) or stochasticity of chemical reactions (intrinsic noise). We find that, no matter what source of the noise is applied, the topologies containing the repressilator with positive auto-regulation show higher robustness of accurate oscillation than those containing the activator-inhibitor oscillator, and additional positive auto-regulation enhances the robustness against noise. Nevertheless, the attenuation of different sources of noise is governed by distinct mechanisms: the parameter variability is buffered by the long period, while the stochasticity of chemical reactions is filtered by the high amplitude. Furthermore, we analyze the noise of a synthetic human nuclear factor κB (NF-κB) signaling network by varying three different topologies, and verify that the addition of a repressilator to the activator-inhibitor oscillator, which leads to the emergence of high-robustness motif—the repressilator with positive auto-regulation, improves the oscillation accuracy in comparison to the topology with only an activator-inhibitor oscillator. These design principles may be applicable to other oscillatory circuits.

The Structural Role of Feed-Forward Loop Motif in Transcriptional Regulatory Networks

2016 ◽  
Vol 21 (1) ◽  
pp. 191-205 ◽  
Author(s):  
Bhanu K. Kamapantula ◽  
Michael L. Mayo ◽  
Edward J. Perkins ◽  
Preetam Ghosh
Keyword(s):  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Feed Forward ◽  
Structural Role ◽  
Feed Forward Loop ◽  
Transcriptional Regulatory

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 Transcriptional Regulatory Networks Associate with Early Stages of Potato Virus X Infection of Solanum tuberosum

2021 ◽  
Vol 22 (6) ◽  
pp. 2837
Author(s):  
Venura Herath ◽  
Jeanmarie Verchot
Keyword(s):  
Potato Virus ◽  
Regulatory Networks ◽  
Potato Virus X ◽  
Early Response ◽  
Pathogen Resistance ◽  
Transcriptional Regulatory Networks ◽  
Unfolded Protein ◽  
Molecular Pattern ◽  
Transcriptional Regulatory ◽  
Protein Response

Potato virus X (PVX) belongs to genus Potexvirus. This study characterizes the cellular transcriptome responses to PVX infection in Russet potato at 2 and 3 days post infection (dpi). Among the 1242 differentially expressed genes (DEGs), 268 genes were upregulated, and 37 genes were downregulated at 2 dpi while 677 genes were upregulated, and 265 genes were downregulated at 3 dpi. DEGs related to signal transduction, stress response, and redox processes. Key stress related transcription factors were identified. Twenty-five pathogen resistance gene analogs linked to effector triggered immunity or pathogen-associated molecular pattern (PAMP)-triggered immunity were identified. Comparative analysis with Arabidopsis unfolded protein response (UPR) induced DEGs revealed genes associated with UPR and plasmodesmata transport that are likely needed to establish infection. In conclusion, this study provides an insight on major transcriptional regulatory networked involved in early response to PVX infection and establishment.

scholarly journals The nuclear receptor HNF4 drives a brush border gene program conserved across murine intestine, kidney, and embryonic yolk sac

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Chen ◽  
Shirley Luo ◽  
Abigail Dupre ◽  
Roshan P. Vasoya ◽  
Aditya Parthasarathy ◽  
...  
Keyword(s):  
Brush Border ◽  
Regulatory Networks ◽  
Critical Role ◽  
Yolk Sac ◽  
Apical Surface ◽  
Transcriptional Regulatory Networks ◽  
Chromatin Looping ◽  
Multiple Organs ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms

AbstractThe brush border is comprised of microvilli surface protrusions on the apical surface of epithelia. This specialized structure greatly increases absorptive surface area and plays crucial roles in human health. However, transcriptional regulatory networks controlling brush border genes are not fully understood. Here, we identify that hepatocyte nuclear factor 4 (HNF4) transcription factor is a conserved and important regulator of brush border gene program in multiple organs, such as intestine, kidney and yolk sac. Compromised brush border gene signatures and impaired transport were observed in these tissues upon HNF4 loss. By ChIP-seq, we find HNF4 binds and activates brush border genes in the intestine and kidney. H3K4me3 HiChIP-seq identifies that HNF4 loss results in impaired chromatin looping between enhancers and promoters at gene loci of brush border genes, and instead enhanced chromatin looping at gene loci of stress fiber genes in the intestine. This study provides comprehensive transcriptional regulatory mechanisms and a functional demonstration of a critical role for HNF4 in brush border gene regulation across multiple murine epithelial tissues.

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