Epigenetic regulation in Drosophila melanogaster via DNA methylation- a systems biology approach. Deepti D. Deobagkar, Chitra Pannikar. Department of Zoology, University of Pune, Pune, India,411007.

   Drosophila melanogaster is a very useful model system to investigate the genotype-phenotype correlations using systems biology approach. Although DNA cytosine methylation is known to be present in Drosophila, the molecular genetic mechanisms regulating methylation machinery and it's components have not yet been unraveled. The physiological role of this important epigenetic modulation remains poorly understood in Drosophila. By utilising high throughput approaches we have investigated the nonCpG methylation in the fruit fly Drosophila. We demonstrate the modulation of methylation levels by employing methylation modulators and several environmental, developmental and epigenetic regulatory factors.In order to study the genome wide methylome, we have developed and utilised a novel method of methylation detection which utilizes a cDNA microarray based approach using anti 5methyl cytosine antibody. This has resulted in elucidation of genome wide methylation map. Gene ontology, involvement of miRNA, epigenetic regulatory proteins in these epigenetic interactions were analysed. This information of methylome and its modulation is utilised to define interactomes and pathways involved in regulatory networks. This method and data generated help us to establish a network of genome wide methylome in any given condition in a biological system. Pathway analysis of these genes revealed statistically significant enrichment of known functions such as DNA binding proteins, signal transduction cascades,etc . The involvement of miRNA in chromatin remodeling and establishing methylation patterns have also been studied in detail. We also demonstrate the utility of methylation modulators in evaluating methylation machinary. The link between processes involved in regulation of alterations in gene expression profiles, protein - protein interaction networks and chromatin structure have been established. This analysis provides important insight into the molecular genetic pathways which govern the process of establishing epigenetic imprints which have not yet been unraveled.