PgmNr D1468: Concentration Dependent Activity of the Bicoid Transcriptional Activator.

Authors:
Colleen Hannon; Shelby Blythe; Eric Wieschaus


Institutes
Princeton University/HHMI, Princeton, NJ.


Keyword: enhancers

Abstract:

In order for embryonic development to proceed correctly and reproducibly, the expression of genes in individual cells must be coordinated with precision. In Drosophila, graded expression of the maternal transcription factor Bicoid (Bcd) provides positional information to pattern the anterior-posterior (AP) axis of the developing embryo. Bcd is known to bind hundreds of sites in the genome, activating target genes at different positions along the AP axis. To measure Bcd binding states at specific concentrations along its gradient, we have developed a series of transgenic lines that express defined uniform concentrations of Bcd. Using chromatin immunoprecipitation for Bcd followed by high throughput sequencing in these transgenic embryos, we group Bcd-bound target regions into several “affinity” classes based on their in vivo occupancy by Bcd at different concentrations. We find that the occupancy of a given target sequence for Bcd is dependent not just on the biochemical affinity of its Bcd binding sites, but its genomic context. Further, we find that some low affinity target regions are dependent on Bcd for maintaining an open chromatin state. This suggests a model in which Bcd is able to influence chromatin structure to gain access to low affinity targets at high concentrations. In contrast, high affinity targets are more accessible either through their native chromatin structure or as a result of other chromatin modifying factors.



Flybase Genetic Index:
1. FlyBase gene symbol: bcd; FBgn: FBgn0000166