TY - JOUR TI - Shadow enhancers can suppress input transcription factor noise through distinct regulatory logic AU - Waymack, Rachel AU - Fletcher, Alvaro AU - Enciso, German AU - Wunderlich, Zeba A2 - Wittkopp, Patricia J A2 - Crocker, Justin VL - 9 PY - 2020 DA - 2020/08/17 SP - e59351 C1 - eLife 2020;9:e59351 DO - 10.7554/eLife.59351 UR - https://doi.org/10.7554/eLife.59351 AB - 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. KW - enhancers KW - gene expression KW - noise KW - development KW - shadow enhancers JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -