The Drosophila Myb and RB/E2F2 complex transcriptionally regulates cytokinesis

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The Myb gene family plays a role in several types of human cancers. For example, high expression levels of c-Myb in colon cancer and B-Myb in breast cancer correlated with poor prognosis for the patient. B-Myb, the vertebrate homolog of invertebrate Myb, activates transcription of mitotic genes. In Drosophila, mutation of Myb reduced expression of mitotic genes, such as the regulatory kinase genes polo and ial (AurB). Previous studies revealed multiple mitotic defects in Myb mutant cells, including disrupted chromosome condensation and abnormal spindles. I 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 subunits Mip130 or E2F2 suppressed the Myb-null cytokinesis defect. While previous Myb-null mitotic phenotypes were difficult to quantitatively assay, the binucleate phenotype was binary, countable, and had a near zero background level in wild-type tissues. This offered a unique opportunity to use the Myb-null binucleate phenotype to study how the dREAM complex represses transcription. In the absence of Myb, repression by the dREAM complex was sensitive to the decreased dose of the subunits E2F2, Mip120, Caf1, and interestingly Lin-52, which was previously genetically implicated as an activator in the complex. Surprisingly, reducing the dose of His2Av also suppressed the Myb-null binucleate phenotype, suggesting a novel role for this variant histone in transcriptional repression by the dREAM complex.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2012
Issuance monographic
Language English


Associated with DeBruhl, Heather Briana
Associated with Stanford University, Department of Genetics
Primary advisor Lipsick, Joseph Steven, 1955-
Thesis advisor Lipsick, Joseph Steven, 1955-
Thesis advisor Fuller, Margaret
Thesis advisor Sage, Julien
Thesis advisor Stearns, Tim
Advisor Fuller, Margaret
Advisor Sage, Julien
Advisor Stearns, Tim


Genre Theses

Bibliographic information

Statement of responsibility Heather Briana DeBruhl.
Note Submitted to the Department of Genetics.
Thesis Thesis (Ph.D.)--Stanford University, 2012.
Location electronic resource

Access conditions

© 2012 by Heather Briana DeBruhl

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