Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer.

ABSTRACT: A challenge in quantitative biology is to predict output patterns of gene expression from knowledge of input transcription factor patterns and from the arrangement of binding sites for these transcription factors on regulatory DNA. We tested whether widespread thermodynamic models could be used to infer parameters describing simple regulatory architectures that inform parameter-free predictions of more complex enhancers in the context of transcriptional repression by Runt in the early fruit fly embryo. By modulating the number and placement of Runt binding sites within an enhancer, and quantifying the resulting transcriptional activity using live imaging, we discovered that thermodynamic models call for higher-order cooperativity between multiple molecular players. This higher-order cooper

SUBMITTER: Kim YJ 

PROVIDER: S-EPMC9836395 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature