Thursday, February 18, 2010

Negative autoregulation linearizes the dose-response and suppresses the heterogeneity of gene expression.

The main observation here is that negative autoregulation in a TF reduces variation in expression of a downstream gene. The thing I initially found curious about the data is that the no feedback (NF) system displays bi-modality. I imagined that, even if a downstream gene has two modes of expression, with a relatively stable protein, you wouldn't see two distinct steady states. They explain this by invoking slow promoter dynamics. These dynamics would have to be slow indeed seeing that a cell with an active YFP (in the expression mode) that switches to inactive, would take many generations to have reporter expression go back to the no expression mode. I think it's more likely that they are not observing expression at equilibrium, but are instead looking at an induction/no induction population. They grow the cells in CSM Glucose overnight and then in CSM Galactose for 16h.

There's more good stuff in this paper.