Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation.

ABSTRACT: Chromatin accessibility is integral to the process by which transcription factors (TFs) read out cis-regulatory DNA sequences, but it is difficult to differentiate between TFs that drive accessibility and those that do not. Deep learning models that learn complex sequence rules provide an unprecedented opportunity to dissect this problem. Using zygotic genome activation in Drosophila as a model, we analyzed high-resolution TF binding and chromatin accessibility data with interpretable deep learning and performed genetic validation experiments. We identify a hierarchical relationship between the pioneer TF Zelda and the TFs involved in axis patterning. Zelda consistently pioneers chromatin accessibility proportional to motif affinity, whereas patterning TFs augment chromatin accessibility i

SUBMITTER: Brennan KJ 

PROVIDER: S-EPMC10592203 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature