A Model for a Genome-Wide Molecular Readout of the Bicoid Morphogen Gradient

Abstract

In Drosophila, graded expression of the maternal transcription factor Bicoid (Bcd) provides positional information to activate target genes at different positions along the anterior-posterior axis. We have measured the genome-wide binding profile of Bcd using ChIP-seq in embryos expressing single, uniform levels of Bcd protein, and grouped Bcd-bound targets into several “affinity” classes based on occupancy at different concentrations. By measuring the biochemical affinity of target enhancers in these classes in vitro and genome-wide chromatin accessibility by ATAC-seq, we found that the occupancy of target sequences by Bcd is not primarily determined by Bcd binding sites, but by genomic context. Bcd drives an open chromatin state at a subset of its targets. Our data support a model whereby Bcd influences chromatin structure to gain access to low affinity targets at high concentrations, while high affinity targets are found in more accessible chromatin and are bound at low concentrations.