The Drosophila Myb and RB/E2F2 complex transcriptionally regulates cytokinesis
Abstract/Contents
- Abstract
- 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.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| 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 |
Subjects
| 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
- Copyright
- © 2012 by Heather Briana DeBruhl
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