In the March 1 issue of G&D, Dr. Joseph Lipsick (Stanford University) and colleagues demonstrate that proteins encoded by the Myb oncogene and the RB tumor suppressor gene function together in the Drosophila MMB/dREAM complex to epigenetically regulate mitotic cell cycle progression.
Drosophila MMB/dREAM includes proteins encoded by the Myb oncogene and the RB and Mip130/Lin-9 tumor suppressor genes, as well as the E2F2 protein which itself binds to the RB protein. While the complex has been previously shown to regulate progression of cell cycle, this paper is the first demonstration of epigenetic regulation of gene expression by Myb and E2F2-RB via the MMB/dREAM complex.
Dr. Lipsick and colleagues found that Myb and E2F2-RB epigenetically regulate expression of the Polo kinase, a key component of cell cycle progression. Using a GFP-Polo reporter gene construct, the researchers were able to monitor Polo gene expression at the level of a single-cell in Drosophila larval imaginal wing discs. They found that flies deficient in both Myb and E2F2 or both Myb and Mip130 displayed variegated patterns of GFP-Polo expression in the same tissue. Furthermore, these patterns of expression were stably inherited through successive rounds of cell division.
Our studies imply that disruptions of the Myb and RB pathways that occur in most human cancers are likely to cause similar epigenetic changes in gene expression. The use of the model organism Drosophila was key to our work because of the powerful experimental tools, the absence of genetic redundancy, and the very well characterized developmental biology in this system.
|Contact: Heather Cosel-Pieper|
Cold Spring Harbor Laboratory