Extra sex combs, chromatin, and cancer: Exploring epigenetic regulation and tumorigenesis in Drosophila

Developmental genetic studies in Drosophila unraveled the importance of Polycomb group (PcG) and Trithorax group (TrxG) genes in controlling cellular identity. PcG and TrxG proteins form histone modifying complexes that catalyze repressive or activating histone modifications, respectively, and thus maintaining the expression status of homeotic genes. Human orthologs of PcG and TrxG genes are implicated in tumorigenesis as well as in determining the prognosis of individual cancers. Recent whole genome analyses of cancers also highlighted the importance of histone modifying proteins in controlling tumorigenesis. Comprehensive understanding of the mechanistic relationship between histone regulation and tumorigenesis holds the promise of significantly advancing our understanding and management of cancer. It is anticipated that Drosophila melanogaster, the model organism that contributed significantly to our understanding of the functional role of histone regulation in development, could also provide unique insight for our understanding of how histone dysregulation can lead to cancer. In this review, we will discuss several recent advances in this regard.