The Complex Containing Drosophila Myb and RB/E2F2 Regulates Cytokinesis in a Histone H2Av-Dependent Manner

Abstract

In Drosophila, mutation of the oncogene Myb reduced the expression of mitotic genes, such as polo and ial, and caused multiple mitotic defects, including disrupted chromosome condensation and abnormal spindles. We now show that binucleate cells, the hallmark phenotype of cytokinesis failure, accumulate in Myb-null ovarian follicle cell and wing disc epithelia. Myb functions as an activator in the generally repressive Drosophila RBF, E2F2, and Myb (dREAM)/Myb-MuvB complex. Absence of the dREAM subunit Mip130 or E2F2 suppressed the Myb-null cytokinesis defect. Therefore, we used Myb-null binucleate cells as a quantitative phenotypic readout of transcriptional repression by the dREAM complex. In the absence of Myb, the complex was sensitive to the dose of the subunits E2F2, Mip120, Caf1, and Lin-52 but not Mip130 or Mip40. Surprisingly, reduction of the dose of His2Av/H2A.z also suppressed the Myb-null binucleate cell phenotype, suggesting a novel role for this variant histone in transcriptional repression by the dREAM complex.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01401-12.

ACKNOWLEDGMENTS

We thank the members of the Lipsick lab and Andrea Stalker for insightful discussions and help preparing the manuscript. We thank the Bloomington Drosophila Stock Center at Indiana University, Lolli Beall, Mike Botchan, Margaret Fuller, David Glover, Jun-yong Huang, Gary Karpen, Peter Lewis, and Jordan Raff for reagents.

This work was supported by USPHS grant RO1 CA 128836 (to J.S.L.) and NIH training grant 5 T32 HG000044 (to H.D.).