TY - JOUR

T1 - Limit cycles in models of circular gene networks regulated by negative feedback loops

AU - Likhoshvai, Vitaly A.

AU - Golubyatnikov, Vladimir P.

AU - Khlebodarova, Tamara M.

PY - 2020/9/14

Y1 - 2020/9/14

N2 - BACKGROUND: The regulatory feedback loops that present in structural and functional organization of molecular-genetic systems and the phenomenon of the regulatory signal delay, a time period between the moment of signal reception and its implementation, provide natural conditions for complicated dynamic regimes in these systems. The delay phenomenon at the intracellular level is a consequence of the matrix principle of data transmission, implemented through the rather complex processes of transcription and translation.However, the rules of the influence of system structure on system dynamics are not clearly understood. Knowledge of these rules is particularly important for construction of synthetic gene networks with predetermined properties. RESULTS: We study dynamical properties of models of simplest circular gene networks regulated by negative feedback mechanisms. We have shown existence and stability of oscillating trajectories (cycles) in these models. Two algorithms of construction and localization of these cycles have been proposed. For one of these models, we have solved an inverse problem of parameters identification. CONCLUSIONS: The modeling results demonstrate that non-stationary dynamics in the models of circular gene networks with negative feedback loops is achieved by a high degree of non-linearity of the mechanism of the autorepressor influence on its own expression, by the presence of regulatory signal delay, the value of which must exceed a certain critical value, and transcription/translation should be initiated from a sufficiently strong promoter/Shine-Dalgarno site. We believe that the identified patterns are key elements of the oscillating construction design.

AB - BACKGROUND: The regulatory feedback loops that present in structural and functional organization of molecular-genetic systems and the phenomenon of the regulatory signal delay, a time period between the moment of signal reception and its implementation, provide natural conditions for complicated dynamic regimes in these systems. The delay phenomenon at the intracellular level is a consequence of the matrix principle of data transmission, implemented through the rather complex processes of transcription and translation.However, the rules of the influence of system structure on system dynamics are not clearly understood. Knowledge of these rules is particularly important for construction of synthetic gene networks with predetermined properties. RESULTS: We study dynamical properties of models of simplest circular gene networks regulated by negative feedback mechanisms. We have shown existence and stability of oscillating trajectories (cycles) in these models. Two algorithms of construction and localization of these cycles have been proposed. For one of these models, we have solved an inverse problem of parameters identification. CONCLUSIONS: The modeling results demonstrate that non-stationary dynamics in the models of circular gene networks with negative feedback loops is achieved by a high degree of non-linearity of the mechanism of the autorepressor influence on its own expression, by the presence of regulatory signal delay, the value of which must exceed a certain critical value, and transcription/translation should be initiated from a sufficiently strong promoter/Shine-Dalgarno site. We believe that the identified patterns are key elements of the oscillating construction design.

KW - Autorepressor

KW - Circular gene networks

KW - Cycles

KW - Delay argument equations

KW - Feedback loops regulation

KW - Inverse problems

KW - Mathematical modeling

KW - Phase portraits

KW - HES7

KW - PROTEIN

KW - OSCILLATORY EXPRESSION

KW - TRANSCRIPTION

KW - AUTOREGULATION

KW - ROBUST

KW - INTEGRATION HOST FACTOR

KW - CONSTRUCTION

KW - NANOG AUTOREPRESSION

KW - MICF

UR - http://www.scopus.com/inward/record.url?scp=85090873396&partnerID=8YFLogxK

U2 - 10.1186/s12859-020-03598-z

DO - 10.1186/s12859-020-03598-z

M3 - Article

C2 - 32921311

AN - SCOPUS:85090873396

VL - 21

SP - 255

JO - BMC Bioinformatics

JF - BMC Bioinformatics

SN - 1471-2105

IS - Suppl 11

M1 - 255

ER -