Drosophila Myb represses retrotransposition and regulates DNA copy number. Juan Santana¹, Abby Long², Kealie Rogers², Stephen Butcher², Scott McDermontt², J Robert Manak^1,2,3. 1) Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA; 2) Department of Biology, University of Iowa, Iowa City, IA; 3) Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA.

   c-Myb is a proto-oncogene associated with leukemias and lymphomas in birds and mammals. Vertebrates have three representatives of the Myb gene family consisting of A-, B- and c-Myb, all of which encode DNA-binding factors that are important for the proper expression of large numbers of genes including those that regulate cell cycle progression and cell differentiation. Drosophila melanogaster contains a single Myb gene (Dm-Myb), mutants of which die before reaching adulthood. Small interfering RNA (siRNA) knockdown of Dm-Myb in an embryonic Drosophila cell line was shown to prevent the proper expression of genes with prominent roles in coordinating cell division. Along the same lines, Dm-Myb mutant larvae display cell cycle defects such as aneuploidy, aberrant spindle formation, and abnormal numbers of centrosomes. Dm-Myb protein is present in a complex which includes the nucleosome remodeling factor NURF. Through yeast two-hybrid experiments and genetic screens, we show that Dm-Myb is specifically interacting with the major subunit of NURF (NURF301) and that these proteins are co-regulating a large number of genes, including those involved in cell cycle control. More surprising, we show that Dm-Myb and NURF301 are working in concert to repress transcription of LTR retrotransposons, and failure to do so results in large-scale transposition events in the genome. Finally, we show that both proteins are required to repress DNA replication of a multitude of genomic regions in polytene tissue nuclei. Collectively, these data have allowed us to identify two new roles for Dm-Myb in controlling large-scale genomic processes which, when compromised, lead to deleterious effects on genome function.