학술논문

Shadow enhancers can suppress input transcription factor noise through distinct regulatory logic.
Document Type
article
Source
Subject
Embryo
Nonmammalian
Animals
Drosophila
Transcription Factors
Stochastic Processes
Gene Expression Regulation
Developmental
Logic
Female
Male
Enhancer Elements
Genetic
D. melanogaster
chromosomes
computational biology
development
enhancers
gene expression
noise
shadow enhancers
systems biology
Biochemistry and Cell Biology
Language
Abstract
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 the transcriptional dynamics of several Kruppel shadow enhancer configurations in live Drosophila embryos, we showed that 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 also 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.