Compositionality, stochasticity, and cooperativity in dynamic models of gene regulation.
نویسندگان
چکیده
We present an approach for constructing dynamic models for the simulation of gene regulatory networks from simple computational elements. Each element is called a "gene gate" and defines an inputoutput relationship corresponding to the binding and production of transcription factors. The proposed reaction kinetics of the gene gates can be mapped onto stochastic processes and the standard ordinary differential equation (ODE) description. While the ODE approach requires fixing the system's topology before its correct implementation, expressing them in stochastic pi-calculus leads to a fully compositional scheme: network elements become autonomous and only the inputoutput relationships fix their wiring. The modularity of our approach allows to pass easily from a basic first-level description to refined models which capture more details of the biological system. As an illustrative application we present the stochastic repressilator, an artificial cellular clock, which oscillates readily without any cooperative effects.
منابع مشابه
Cooperativity in biological systems
Living organisms can sense and respond to external and internal stimuli. Response isdemonstrated in many forms including modulation of gene expression profiles, motility,secretion, cell death, etc. Nevertheless, all forms share a basic property: they depend on sensingsmall changes in the concentration of an effector molecule or subtle conformational changes ina protein and invoking the appropri...
متن کاملRoles of Chromatin insulators in gene regulation and diseases
With advances in genetic science, the dynamic structure of eukaryotic genome is considered as basis of gene expression regulation. Long-distance communication between regulatory elements and target promoters is critical and the mechanisms responsible for this connection are just starting to emerge. Chromatin insulators are key determinants of proper gene regulation and precise organization of c...
متن کاملAsynchronous Stochastic Boolean Networks as Gene Network Models
Logical models have widely been used to gain insights into the biological behavior of gene regulatory networks (GRNs). Most logical models assume a synchronous update of the genes' states in a GRN. However, this may not be appropriate, because each gene may require a different period of time for changing its state. In this article, asynchronous stochastic Boolean networks (ASBNs) are proposed f...
متن کاملPseudo-Random Fluctuations, Stochastic Cooperativity and Burstiness in Dynamically Unstable High-Dimensional Biochemical Networks
Two major approaches are known in the field of stochastic dynamics of intra-cellular biochemical networks. The first one places the focus of attention on the fact that many biochemical constituents vitally important for the network functionality may be present only in small quantities within the cell, and therefore the regulatory process is essentially discrete and prone to relatively big fluct...
متن کاملA model for the cooperative binding of eukaryotic regulatory proteins to nucleosomal target sites.
The mechanism by which gene regulatory proteins gain access to their DNA target sequences in chromatin is not known. We recently showed that nucleosomes are intrinsically dynamic, transiently exposing their DNA to allow sequence-specific protein binding even at buried sites. Here we show that this dynamic behaviour provides a mechanism for cooperativity (synergy) in the binding of two or more p...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- HFSP journal
دوره 2 1 شماره
صفحات -
تاریخ انتشار 2008