Title
Reshaping the epigenetic landscape during early flower development: induction of attractor transitions by relative differences in gene decay rates.
Abstract
Gene regulatory network (GRN) dynamical models are standard systems biology tools for the mechanistic understanding of developmental processes and are enabling the formalization of the epigenetic landscape (EL) model.In this work we propose a modeling framework which integrates standard mathematical analyses to extend the simple GRN Boolean model in order to address questions regarding the impact of gene specific perturbations in cell-fate decisions during development.We systematically tested the propensity of individual genes to produce qualitative changes to the EL induced by modification of gene characteristic decay rates reflecting the temporal dynamics of differentiation stimuli. By applying this approach to the flower specification GRN (FOS-GRN) we uncovered differences in the functional (dynamical) role of their genes. The observed dynamical behavior correlates with biological observables. We found a relationship between the propensity of undergoing attractor transitions between attraction basins in the EL and the direction of differentiation during early flower development - being less likely to induce up-stream attractor transitions as the course of development progresses. Our model also uncovered a potential mechanism at play during the transition from EL basins defining inflorescence meristem to those associated to flower organs meristem. Additionally, our analysis provided a mechanistic interpretation of the homeotic property of the ABC genes, being more likely to produce both an induced inter-attractor transition and to specify a novel attractor. Finally, we found that there is a close relationship between a gene's topological features and its propensity to produce attractor transitions.The study of how the state-space associated with a dynamical model of a GRN can be restructured by modulation of genes' characteristic expression times is an important aid for understanding underlying mechanisms occurring during development. Our contribution offers a simple framework to approach such problem, as exemplified here by the case of flower development. Different GRN models and the effect of diverse inductive signals can be explored within the same framework. We speculate that the dynamical role of specific genes within a GRN, as uncovered here, might give information about which genes are more likely to link a module to other regulatory circuits and signaling transduction pathways.
Year
DOI
Venue
2015
10.1186/s12918-015-0166-y
BMC Systems Biology
Keywords
Field
DocType
Gene regulatory network, Epigenetic landscape, Attractor landscape, Differentiation, Flower development, Attractor transitions
Attractor,Gene,Biology,Systems biology,Bioinformatics,Gene regulatory network,Epigenetics
Journal
Volume
Issue
ISSN
9
1
1752-0509
Citations 
PageRank 
References 
3
0.47
5
Authors
3
Name
Order
Citations
PageRank
Jose Davila-Velderrain140.88
Carlos Villarreal230.47
Elena R Alvarez-Buylla330.47