Paris/FFL

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Fig. 1 : Structure of a type 1 coherent Feed Forward Loop

A Feed-Forward Loop is a genetic network composed of three nodes. This strong network motif is composed of a transcription factor X that regulates a second transcription factor, Y, and both X and Y regulate Z (Figure 1).

Depending on the type of regulations between the different nodes, we can define eight types of FFL that can be classified into two groups : coherent and incoherent FFLs. In coherent FFLs, the indirect path has the same overall sign as the direct path. The most abundant FFL is the type-1 coherent FFL (C1-FFL) (Figure 1).

In addition to the signs of the edges, to understand the dynamics of the FFL, we must also know how the inputs from the two regulators X and Y are integrated at the promoter of the gene Z. Uri ALON considers that there are two biologically reasonable logic functions : "AND" logic, in which both X and Y activities are need to be high in order to turn on Z expression and "OR" logic in which either X or Y is sufficient (Figure 2).



Fig. 2 : The C1-FFL with OR logic in the flagella system of E. coli.

If the input function of the promoter of the gene Z is "OR", Z is expressed when X activity is high. There is no delay following the expression of X. But when X is not expressed anymore, its concentration decreases and reach the activation threshold of Y and Z. Y is not expressed anymore but as the concentration decreases, Z is still expressed. The OR-gate C1-FFL allow the gene Z to be expressed about one more hour after the gene X is OFF. (Figure 3)

Fig. 3 : Promoter dynamics after an OFF step of X, in the presence of Y. The results are shown for the wild-type bacterium, and for a bacterium in which the gene for Fli1 was deleted from the genome. The FFL generates a delay after an OFF step of X

Bibliography :

1. Shen-Orr et al. (2002)

2. Mangan et al. (2003)

3. Mangan et al. (2003)

4. Kalir et al. (2005)