Assume we have a synthetic construct with a minimal (inducible) promoter that requires activation for significant transcription to occur. Realistically, how important is the distance between an activator binding site and a promoter - would placing the binding site closer to the promoter lead to significantly stronger activation, or more robust system behavior?
In some genomics-related models I saw authors assigned weights to binding sites based on position (orientation and distance from the promoter); the general idea was that binding sites farther away could have a weaker influence on transcription. This can be modeled e.g. by decreasing the binding affinity. But that was genomics, and I'm unsure how much of that has any relevance in smaller scale plasmid constructs.
For example, suppose we have a highly specific binding site (e.g. a TALE binding site) upstream of the promoter:
In Fig.1, the binding site A is only e.g. 40 bp away from the promoter. In Fig.2, it is e.g. 5000-7000 bp away. Should I expect this to make a noticeable difference? Would the same apply if it would be a constitutive promoter, with a repressor instead of an activator? What about more complex networks, could the answer change?