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Fig. 6. Protein complexes mediate dampening of stochastic oscillations. By setting the value of a given entity to a random
number, the overall response of the network to stochastic oscillations is observed. In this case the value of a given entity is set to
oscillate at random between 0 and 1 under the given initial conditions. The only cases found to be sensitive to these oscillations
are the random activation of AP2, which does not form a protein complex under sepal and stamen initial conditions, a situation
which disrupts expression patterns.
oscillations on target entities is also reduced. This effect arises if one of the partners of a dimer complex
has an aberrant expression, but the other remains under normal control, the concentration of the dimer
will show an oscillation whose magnitude is reduced with respect to the monomer. This dampening effect
is even more pronounced for higher-order complexes. The corresponding variation of the concentration
of the final transcription factor complexes is found to be about one fifth of the variation of the chosen
single monomer.
Changes in organ-specific steady states of gene expression were observed when random noise on
the AP2 protein concentration was introduced. Under the initial conditions for sepal development,
AG
was transiently activated because the concentration of AP2 reached a value under the activity threshold
that is required for inhibition of
AG
. AG, in turn, inhibited the production of AP1 which resulted in
the disappearance of the sepal complex (Fig. 6). In the case of petal and stamen conditions, the petal
complex is formed at relatively low concentration. Here the petal complex further inhibits the expression
of
AG
, resulting in an indirect activation effect on AP1 which, while it does not recover the expression
pattern of the original model, allows for sustained AP1 production and a low level formation of the
petal complex SEP/AP1/AP3/PI. It is important to note that if a basal level of AP2 protein expression is
kept, the inhibitory effect of stochastic fluctuations of AP2 on sepal development is absent. Stochastic
fluctuation of AG leads to defects in organ-specific protein complexes: the stamen complex is formed
instead of the petal complex and the carpel complex instead of the sepal complex, leading to floral
homeotic conversions. The simulation thus mimics a situation in which AG is ectopically expressed.
Notably, the sensitivity of petal and sepal steady-states of gene expression are in line with data suggesting
that
AG
is repressed by multiple mechanisms in developing sepals and petals, which have for sake of
focus and simplicity not been included in our model [see, e.g., Krizek
et al.
, 2000; Bao
et al.
, 2004].
The role of transcription factor complexes in stabilizing network dynamics
According to the 'floral quartet model' [Theissen and Saedler, 2001], floral homeotic proteins belonging
to the MADS-box family assemble in a combinatorial fashion into organ-specific, higher-order protein
complexes. In order to test whether heteromeric protein complexes could play a role in the stabilization
