Chromosome-wide gene regulation in Drosophila
Chromosomal instability which involves the deletion and duplication of chromosomes or chromosome parts is a common feature of cancers. Still, how regulation of whole-chromosomes or large-chromosome-domains is affected by deficiencies or chromosome loss (e.g. somatic elimination) is largely unknown. We believe that our chromosome 4 model is very suitable to study domain and whole chromosome gene regulation. Our main goal is to contribute to the understanding of targeting, function and evolution of chromosome-wide gene regulation. In particular, we focus on exploring autosome-specific gene regulation by the continued study of the protein POF (Painting of Fourth) in Drosophila.
Chromosome-wide targeting have until recently been consider only as a mechanism to equalize the transcriptional activity of the single male X-chromosome with that of the two female X-chromosomes, i.e., dosage compensation. Our discovery of the chromosome specific protein Painting-of-Fourth (POF) is the first example of a chromosome-wide targeting mechanism for an autosome. We have recently shown that POF and heterochromatin-protein-1 (HP1) are involved in the global regulation of the 4th chromosome in Drosophila. POF binding is dependent on heterochromatin and POF and HP1 bind interdependently to the 4th chromosome. We have proposed a balancing mechanism involving POF and HP1 that provides a feed-back system for fine-tuning expression status on the 4th chromosome. Balancing mechanisms may be a general way to regulate gene expression at a chromosome-wide level. The continued analysis of chromosome-wide regulation focuses on three different questions:
1. Generality, function and mechanisms for chromosome targeting and regulation.
2. Establishment and propagation of chromatin structure within and between chromosomes.
3. Evolution of chromosome-wide targeting mechanisms.
At present, POF is likely to represent the most compelling example of a chromosome targeting mechanism adapted for targeting of regulatory factors to an autosome. We believe that our work on POF has the potential to make major contribution to our understanding of chromosome-wide regulatory complexes, their composition, function and evolution.