scholarly journals The role of time delays in P53 gene regulatory network stimulated by growth factor

2020 ◽  
Vol 17 (4) ◽  
pp. 3794-3835
Author(s):  
Changyong Dai ◽  
◽  
Haihong Liu ◽  
Fang Yan ◽  
Keyword(s):  
Growth Factor ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Time Delays ◽  
P53 Gene ◽  
Gene Regulatory

scholarly journals IGFBP2 Is a Potential Master Regulator Driving the Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme

2021 ◽  
Vol 12 ◽  
Author(s):  
Manasa Kalya ◽  
Alexander Kel ◽  
Darius Wlochowitz ◽  
Edgar Wingender ◽  
Tim Beißbarth
Keyword(s):  
Growth Factor ◽  
Glioblastoma Multiforme ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Epithelial To Mesenchymal Transition ◽  
Binding Protein ◽  
Oncostatin M ◽  
Mesenchymal Transition ◽  
Short Survival ◽  
Gene Regulatory

Only 2% of glioblastoma multiforme (GBM) patients respond to standard therapy and survive beyond 36 months (long-term survivors, LTS), while the majority survive less than 12 months (short-term survivors, STS). To understand the mechanism leading to poor survival, we analyzed publicly available datasets of 113 STS and 58 LTS. This analysis revealed 198 differentially expressed genes (DEGs) that characterize aggressive tumor growth and may be responsible for the poor prognosis. These genes belong largely to the Gene Ontology (GO) categories “epithelial-to-mesenchymal transition” and “response to hypoxia.” In this article, we applied an upstream analysis approach that involves state-of-the-art promoter analysis and network analysis of the dysregulated genes potentially responsible for short survival in GBM. Binding sites for transcription factors (TFs) associated with GBM pathology like NANOG, NF-κB, REST, FRA-1, PPARG, and seven others were found enriched in the promoters of the dysregulated genes. We reconstructed the gene regulatory network with several positive feedback loops controlled by five master regulators [insulin-like growth factor binding protein 2 (IGFBP2), vascular endothelial growth factor A (VEGFA), VEGF165, platelet-derived growth factor A (PDGFA), adipocyte enhancer-binding protein (AEBP1), and oncostatin M (OSMR)], which can be proposed as biomarkers and as therapeutic targets for enhancing GBM prognosis. A critical analysis of this gene regulatory network gives insights into the mechanism of gene regulation by IGFBP2 via several TFs including the key molecule of GBM tumor invasiveness and progression, FRA-1. All the observations were validated in independent cohorts, and their impact on overall survival has been investigated.

scholarly journals Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network

2017 ◽  
Vol 114 (23) ◽  
pp. 5800-5807 ◽  
Author(s):  
William J. R. Longabaugh ◽  
Weihua Zeng ◽  
Jingli A. Zhang ◽  
Hiroyuki Hosokawa ◽  
Camden S. Jansen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
Notch Signaling ◽  
Gene Regulatory Network ◽  
Cell Fate ◽  
Regulatory Network ◽  
T Cell Development ◽  
Cell Specification ◽  
Gene Regulatory

T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment and relate them to other regulomes. We show that both activation and repression target genes can be bound by Bcl11b in vivo, and that Bcl11b effects overlap with E2A-dependent effects. The newly clarified role of Bcl11b distinguishes discrete components of commitment, resolving how innate lymphoid, myeloid, and dendritic, and B-cell fate alternatives are excluded by different mechanisms.

Impacts of Multiple Time Delays on a Gene Regulatory Network Mediated by Small Noncoding RNA

2020 ◽  
Vol 30 (05) ◽  
pp. 2050069
Author(s):  
Ming Liu ◽  
Fanwei Meng ◽  
Dongpo Hu
Keyword(s):  
Hopf Bifurcation ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Time Delays ◽  
Noncoding Rna ◽  
Multiple Time ◽  
Normal Form Theory ◽  
Small Noncoding Rna ◽  
Multiple Time Delays ◽  
Gene Regulatory

In this paper, the impacts of multiple time delays on a gene regulatory network mediated by small noncoding RNA is studied. By analyzing the associated characteristic equation of the corresponding linearized system, the asymptotic stability of the positive equilibrium is investigated and Hopf bifurcation is demonstrated. Furthermore, the explicit formulae for determining the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions are given by the center manifold theorem and the normal form theory for functional differential equations. Finally, some numerical simulations are demonstrated for supporting the theoretical results.

scholarly journals Architecture and dynamics of the jasmonic acid gene regulatory network

2016 ◽  
Author(s):  
Richard J. Hickman ◽  
Marcel C. Van Verk ◽  
Anja J.H. Van Dijken ◽  
Marciel Pereira Mendes ◽  
Irene A. Vos ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Jasmonic Acid ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Network Modules ◽  
Time Series Analyses ◽  
Gene Regulatory ◽  
Ja Signaling ◽  
Signaling Components

ABSTRACTThe phytohormone jasmonic acid (JA) is a critical regulator of plant growth and defense. To significantly advance our understanding of the architecture and dynamics of the JA gene regulatory network, we performed high-resolution RNA-Seq time series analyses of methyl JA-treated Arabidopsis thaliana. Computational analysis unraveled in detail the chronology of events that occur during the early and later phases of the JA response. Several transcription factors, including ERF16 and bHLH27, were uncovered as early components of the JA gene regulatory network with a role in pathogen and insect resistance. Moreover, analysis of subnetworks surrounding the JA-induced transcription factors ORA47, RAP2.6L, and ANAC055 provided novel insights into their regulatory role of defined JA network modules. Collectively, our work illuminates the complexity of the JA gene regulatory network, pinpoints to novel regulators, and provides a valuable resource for future studies on the function of JA signaling components in plant defense and development.

Multiple Time Delays Induced Dynamics of p53 Gene Regulatory Network

2021 ◽  
Vol 31 (15) ◽  
Author(s):  
Yuanhong Bi ◽  
Yanan Li ◽  
Jianmin Hou ◽  
Quansheng Liu
Keyword(s):  
Time Delay ◽  
Equilibrium Point ◽  
Regulatory Network ◽  
Time Delays ◽  
P53 Gene ◽  
Positive Equilibrium ◽  
Multiple Time ◽  
Multiple Time Delays ◽  
Gene Regulatory ◽  
Positive Equilibrium Point

p53 dynamics plays an important role in determining cell arrest or apoptosis upon DNA damage response. In this paper, based on a p53 gene regulatory network composed of its core regulator ATM, Mdm2 and Wip1, the effect of multiple time delays in transcription and translation of Mdm2 and Wip1 gene expression on p53 dynamics are investigated through theoretical and numerical analyses. The stability of the positive equilibrium point and the existence of Hopf bifurcation are demonstrated through analyzing the associated characteristic equation of the corresponding linearized system in five cases. Detailed numerical simulations and bifurcation analyses are performed to support the theoretical results. The results show that with the increase of a time delay, the positive equilibrium point becomes unstable, and the p53 dynamics presents an oscillating state. These results reveal that time delay has a significant impact on p53 dynamics and may provide a useful insight into developing anti-cancer therapy.

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