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Enciso, G.

Publications and source records attributed to Enciso, G..

2 recordsLinked to original sources

Bounds on the Ultrasensitivity of Biochemical ReactionCascades

The ultrasensitivity of a dose response function can be quantifiably defined using the generalized Hill coefficient of the function. Our group examined an upper bound for the Hill coefficient of the composition of two functions, namely the product of their individual Hill coefficients. We proved that this upper bound holds for compositions of Hill functions, and that there are instances of counterexamples that exist for more general sigmoidal functions. Additionally, we tested computationally other types of sigmoidal functions, such as the logistic and inverse trigonometric functions, and we provided evidence that in these cases the inequality also holds. We show that in large generality there is a limit to how ultrasensitive the composition of two functions can be, which has applications to understanding signaling cascades in biochemical reactions.

systems biology↗

Shadow enhancers suppress input transcription factor noise through distinct regulatory logic

Shadow enhancers, groups of seemingly redundant enhancers, are found in a wide range of organisms and are critical for robust developmental patterning. However, their mechanism of action is unknown. We hypothesized that shadow enhancers drive consistent expression levels by buffering upstream noise through a separation of transcription factor (TF) inputs at the individual enhancers. By measuring transcriptional dynamics of several Kruppel shadow enhancer configurations in live Drosophila embryos, we showed individual member enhancers act largely independently. We found that TF fluctuations are an appreciable source of noise that the shadow enhancer pair can better buffer than duplicated enhancers. The shadow enhancer pair is uniquely able to maintain low levels of expression noise across a wide range of temperatures. A stochastic model demonstrated the separation of TF inputs is sufficient to explain these findings. Our results suggest the widespread use of shadow enhancers is partially due to their noise suppressing ability.

systems biology↗