TY - JOUR
T1 - Retroactivity effects dependency on the transcription factors binding mechanisms
AU - Pantoja-Hernández, Libertad
AU - Álvarez-Buylla, Elena
AU - Aguilar-Ibáñez, Carlos F.
AU - Garay-Arroyo, Adriana
AU - Soria-López, Alberto
AU - Martínez-García, Juan Carlos
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/12/7
Y1 - 2016/12/7
N2 - Downstream connection effects on transcription are caused by retroactivity. When biomolecular dynamical systems interconnect retroactivity is a property that becomes important. The biological functional meaning of these effects is increasingly becoming an area of interest. Downstream targets, which are operator binding sites in transcriptional networks, may induce behaviors such as ultrasensitive responses or even represent an undesired issue in regulation. To the best of our knowledge, the role of the binding mechanisms of transcription factors in relation to minimizing – or enhancing – retroactivity effects has not been previously addressed. Our aim is to evaluate retroactivity effects considering how the binding mechanism impacts the number of free functional transcription factor (FFTF) molecules using a simple model via deterministic and stochastic simulations. We study four transcription factor binding mechanisms (BM): simple monomer binding (SMB), dimer binding (DB), cooperative sequential binding (CSB) and cooperative sequential binding with dimerization (CSB_D). We consider weak and strong binding regimes for each mechanism, where we contrast the cases when the FFTF is bound or unbound to the downstream loads. Upon interconnection, the number of FFTF molecules changed less for the SMB mechanism while for DB they changed the most. Our results show that for the chosen mechanisms (in terms of the corresponding described dynamics), retroactivity effects depend on transcription binding mechanisms. This contributes to the understanding of how the transcription factor regulatory function—such as decision making—and its dynamic needs for the response, may determine the nature of the selected binding mechanism.
AB - Downstream connection effects on transcription are caused by retroactivity. When biomolecular dynamical systems interconnect retroactivity is a property that becomes important. The biological functional meaning of these effects is increasingly becoming an area of interest. Downstream targets, which are operator binding sites in transcriptional networks, may induce behaviors such as ultrasensitive responses or even represent an undesired issue in regulation. To the best of our knowledge, the role of the binding mechanisms of transcription factors in relation to minimizing – or enhancing – retroactivity effects has not been previously addressed. Our aim is to evaluate retroactivity effects considering how the binding mechanism impacts the number of free functional transcription factor (FFTF) molecules using a simple model via deterministic and stochastic simulations. We study four transcription factor binding mechanisms (BM): simple monomer binding (SMB), dimer binding (DB), cooperative sequential binding (CSB) and cooperative sequential binding with dimerization (CSB_D). We consider weak and strong binding regimes for each mechanism, where we contrast the cases when the FFTF is bound or unbound to the downstream loads. Upon interconnection, the number of FFTF molecules changed less for the SMB mechanism while for DB they changed the most. Our results show that for the chosen mechanisms (in terms of the corresponding described dynamics), retroactivity effects depend on transcription binding mechanisms. This contributes to the understanding of how the transcription factor regulatory function—such as decision making—and its dynamic needs for the response, may determine the nature of the selected binding mechanism.
KW - Binding processes
KW - Dimerization
KW - ODE simulations
KW - Regulation
KW - SSA
KW - Sequential binding
UR - http://www.scopus.com/inward/record.url?scp=84988885770&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2016.08.012
DO - 10.1016/j.jtbi.2016.08.012
M3 - Artículo
SN - 0022-5193
VL - 410
SP - 77
EP - 106
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
ER -