Chromosome-wide gene regulation and chromosome specific adaptations

In fruit flies, two chromosome-wide gene regulatory systems have been characterised:The dosage compensation mechanisms that equalize the transcriptional activity of the single male X-chromosome and the two female X-chromosomes.The system that we have discovered, POF (Painting of Fourth): the chromosome-specific targeting and regulation of genes located on the 4th chromosome.At present, POF is the most compelling example of a chromosome targeting mechanism adapted to the long-range targeting of regulatory factors to a specific autosome.

POF represents a novel model with which to study chromosome-specific regulation and a challenging new biological concept, i.e. chromosome-specific functions.

Our main goal is to broaden our understanding of such functions using the protein POF and the dosage compensation mechanisms as models.

Our proposal is focused on:Deciphering the targeting mechanisms used by chromosome-wide gene regulatory complexes in particular and epigenetic regulators in general.Delineating the link that we have discovered between chromosome-wide targeting and chromosome segregation.Understanding the evolution of chromosome-specific gene targeting and regulation, sex-chromosomes and the roles of heterochromatin and RNA interactions in these processes.We believe that our work will make major new contributions to our understanding of epigenetic regulatory complexes: how they are targeted and established, how they regulate targeted genes and how they evolve.