Combining modelling and experimental approaches to explain how calcium signatures are decoded by calmodulin‐binding transcription activators (CAMTAs) to produce specific gene expression responses

Summary Experimental data show that Arabidopsis thaliana is able to decode different calcium signatures to produce specific gene expression responses. It is also known that calmodulin‐binding transcription activators (CAMTAs) have calmodulin (CaM)‐binding domains. Therefore, the gene expression responses regulated by CAMTAs respond to calcium signals. However, little is known about how different calcium signatures are decoded by CAMTAs to produce specific gene expression responses. A dynamic model of Ca2+–CaM–CAMTA binding and gene expression responses is developed following thermodynamic and kinetic principles. The model is parameterized using experimental data. Then it is used to analyse how different calcium signatures are decoded by CAMTAs to produce specific gene expression responses. Modelling analysis reveals that: calcium signals in the form of cytosolic calcium concentration elevations are nonlinearly amplified by binding of Ca2+, CaM and CAMTAs; amplification of Ca2+ signals enables calcium signatures to be decoded to give specific CAMTA‐regulated gene expression responses; gene expression responses to a calcium signature depend upon its history and accumulate all the information during the lifetime of the calcium signature. Information flow from calcium signatures to CAMTA‐regulated gene expression responses has been established by combining experimental data with mathematical modelling.


Article acceptance date: 26 March 2015
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Fig. S6
The effects of varying the total CaM concentration on the amplification of Ca 2+ signals.

Fig. S7
The effects of simultaneously varying all five adjustable parameters (example 1).

Fig. S8
The effects of simultaneously varying all five adjustable parameters (example 2).

Fig. S17
Gene expression accumulates all information during the lifetime of the prolonged calcium signature (Fig. 4a).

Fig. S18
The reconstructed piecewise calcium signature with T=8s.

Fig. S19
The reconstructed piecewise calcium signature with T=200s.

Fig. S20
Effects of the number of calcium spikes on fold change in gene expression Notes S1 Modelling equations.

Fig. S1
The effects of varying K d of R33, , by changing kon. When changes, the following relationship must be valid due to thermodynamic constraints: In order to maintain the above relationships, changes, the following relationship must be valid due to thermodynamic constraints: In order to maintain the above relationships, changes, the following relationship must be valid due to thermodynamic constraints: In order to maintain the above relationships, when changes, the following relationship must be valid due to thermodynamic constraints: In order to maintain the above relationships, when

Fig. S7
The effects of simultaneously varying all five adjustable parameters (example 1). Solid red line: total CaM concentration is 1000 µM, total CAMTA concentration: 1000 µM , the cooperative binding between CaM and CAMTA in the presence of Ca 2+ due to on binding rate (Q in Eqn 3): 100, the cooperative binding between CaM and CAMTA in the presence of Ca 2+ (P in Eqn 2): 0.01, on rate for the binding between the Ca 2+ -CaM complex and CAMTA (k on(R14) ): 100 µM -1 s -1 . Dashed black line: total CaM concentration is 0.1 µM, total CAMTA concentration: 0.1 µM , the cooperative binding between CaM and CAMTA in the presence of Ca 2+ due to on binding rate (Q in Eqn 3): 0.01, the cooperative binding between CaM and CAMTA in the presence of Ca 2+ (P in Eqn 2): 1, on rate for the binding between the Ca 2+ -CaM complex and CAMTA (k on(R14) ): 0.01 µM -1 s -1 . Reference value (Fig. 2): total CaM concentration is 10 µM, total CAMTA concentration: 10 µM , the cooperative binding between CaM and CAMTA in the presence of Ca 2+ due to on binding rate (Q in Eqn 3): 1, the cooperative binding between CaM and CAMTA in the presence of Ca 2+ (P in Eqn 2): 0.1, on rate for the binding between the Ca 2+ -CaM complex and CAMTA (k on(R14) ): 1 µM -1 s -1 .

Fig. S8
The effects of simultaneously varying all five adjustable parameters (example 2). Solid red line: total CaM concentration is 0.1 µM, total CAMTA concentration: 1000 µM, the cooperative binding between CaM and CAMTA in the presence of Ca 2+ due to on binding rate (Q in Eqn 3): 0.01, the cooperative binding between CaM and CAMTA in the presence of Ca 2+ (P in Eqn 2): 0.01, on rate for the binding between the Ca 2+ -CaM complex and CAMTA (k on(R14) ): 100 µM -1 s -1 . Dashed black line: total CaM concentration is 1000 µM, total CAMTA concentration: 0.1 µM , the cooperative binding between CaM and CAMTA in the presence of Ca 2+ due to on binding rate (Q in Eqn 3): 100, the cooperative binding between CaM and CAMTA in the presence of Ca 2+ (P in Eqn 2): 1, on rate for the binding between the Ca 2+ -CaM complex and CAMTA (k on(R14) ): 0.01 µM -1 s -1 . Reference value (Fig. 2): total CaM concentration is 10 µM, total CAMTA concentration: 10 µM , the cooperative binding between CaM and CAMTA in the presence of Ca 2+ due to on binding rate (Q in Eqn 3): 1, the cooperative binding between CaM and CAMTA in the presence of Ca 2+ (P in Eqn 2): 0.1, on rate for the binding between the Ca 2+ -CaM complex and CAMTA (k on(R14) ): 1 µM -1 s -1 .

Fig. S14
The effects of varying Hill coefficient (n) on fold change of gene expression. Binding affinity (K d ) is 1.1e-2 µM. Red line: n=2 (reference value (Fig. 6)). Blue line: n=1. Green line: n=3.  actual fold change of gene expression for transient calcium signature (Fig. 3a). Gene expression accumulates all information from the transient calcium signature (Fig. 3a) in a similar manner to the first cycle of Fig. 7 (points I-IV), as analysed in the main text. actual fold change of gene expression for prolonged calcium signature (Fig. 4a). Gene expression accumulates all information from the prolonged calcium signature (Fig. 4a) in a similar manner to the first cycle of Fig. 7 (points I-IV), as analysed in the main text.

Fig. S18
The reconstructed piecewise calcium signature with T=8 s and all other parameters are exactly the same as in Fig. 8(a)  =0.10 µM).