Analysis of biochemical mechanisms provoking differential spatial expression in Hh target genes

Abstract

This work analyses the transcriptional effects of some biochemical mechanisms proposed in previous literature which attempts to explain the differential spatial expression of Hedgehog target genes involved in Drosophila development. Specifically, the expression of decapentaplegic and patched, genes whose transcription is believed to be controlled by the activator and repressor forms of the transcription factor Cubitus interruptus (Ci). This study is based on a thermodynamic approach which provides binding equilibrium weighted average rate expressions for genes controlled by transcription factors competing and (possibly) cooperating for common binding sites, in the same way that Ci's activator and repressor forms might do. These expressions are refined to produce simpler equivalent formulae allowing their mathematical analysis. Thanks to this, we can evaluate the correlation between several molecular processes and biological features observed at tissular level. In particular, we will focus on how high/low/differential affinity and null/total/partial cooperation modify the activation/repression regions of the target genes or provoke signal modulation.