Comparative analysis of Su(var) chromatin regulators in Drosophila and the mouse

• Applicants: Professor Dr. Thomas Jenuwein; Professor Dr. Gunter Reuter (†)
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277626540

Heterochromatin has important functions in protecting genome integrity, maintaining cell identity and stabilizing gene expression programs. During the last 15 years several epigenetic factors involved in heterochromatin formation and maintenance have been described. In particular, screens for Su(var) mutations of PEV (position effect variegation) in Drosophila have proven instrumental in identifying core heterochromatin components, most of which are conserved in higher eukaryotes. Despite these significant advances, it is important to note that only ~25% of the about 100 Su(var) loci have been molecularly defined, with the remaining unknown loci estimated to encode for approximately 70 novel heterochromatin regulators. Here, we propose to use a genome-wide sequencing approach to rapidly map novel Su(var) mutations that were generated in isogenic Drosophila strains. This analysis is expected to result in the identification of about 50 novel SU(VAR) factors. Functional analysis in Drosophila and mouse will focus on selected conserved Su(var) genes and will address their molecular roles in genome-wide gene silencing and heterochromatin formation. The proposed research plan will provide significant new insights into the molecular basis of chromatin partitioning and conserved aspects of heterochromatin regulation in Drosophila and mammals.

• DFG Programme: Research Grants