Distinct roles for COMPASS core subunits Set1, Trx, and Trr in the epigenetic regulation of Drosophila heart development

This study investigated the role Complex of Proteins Associated with Set1 (COMPASS) in heart development. These are evolutionarily highly conserved multiprotein complexes required for H3K4 methylation. In Drosophila, their core subunits are Set1, Trx, and Trr. We studied flies deficient for either of these three subunits their hearts. These flies showed high lethality at eclosion (emergence of adult flies from their pupal case) and significantly shortened lifespans for the adults that did emerge. Furthermore, their hearts showed reduced H3K4 monomethylation (H3K4me1) and dimethylation (H3K4me2), and significantly altered gene expression patterns. The data revealed that each of the COMPASS core subunits (Set1, Trx, and Trr) control methylation of different sets of genes with distinct temporal activity: Set1 throughout, whereas Trr was active early and Trx at later stages of heart development. We found that many metabolic pathways were active early in development and throughout, while muscle and heart differentiation processes were methylated during later stages of development. Taken together, the findings demonstrate the importance of COMPASS complexes during heart development, therewith supporting their implication in congenital heart diseases. Overall design: To investigate the gene expression patterns regulated by Set1, Trx, and Trr. We employed the Drosophila UAS-Gal4 system combined with RNAi knockdown. We used twist (twi)-Gal4 to tissue knockdown Set1, trx, or trr specifically in the Drosophila heart. We then performed gene expression profiling analysis using data obtained from RNA-Seq of three different samples for each genotype. Comparative gene expression profiling analysis of RNA-Seq data for wildtype and its knock-down (RNAi) derivatives (Set1, trx, and trr).