Transcriptional and cell cycle control of erythropoiesis by E2F4

Funded Activity Summary

The balance in the number of cells in our body is a carefully regulated process which, when disturbed, can lead to a number of life-threatening diseases such as cancer. Through genetic studies in the mouse, we previously identified E2F4 as a protein that is required for the correct number of red blood cells in the body. Lack of E2F4 results in anaemia in the mouse embryo. We have studied these mice as a model to understand how cell production in the body can be controlled. In recent studies, we have identified proliferation defects and in particular cell division cycle defects as the major cause for the decreased production of red blood cells in the embryo. In addition, we have utilised gene microarray technology to survey which genes change in the absence of E2F4 by comparing gene expression profiles in normal and E2F4 deficient mice. These studies have identified a large number of genes that could be molecular targets for E2F4 and whose defective expression could be ultimately responsible for the anaemia of these mice. Importantly, our data suggests a completely novel function for E2F4 in controlling the switching on of genes required for cell division. In this proposal, we describe approaches to characterise how E2F4 controls the cell division cycle to identify the exact process(es) it may control such as DNA replication or separation of chromosomes into daughter cells. We will also test our hypothesis for a novel role for E2F4 in being able to switch on genes in nucleated red blood cell. Finally, we describe gene microarray experiments and a new promoter microarray approach to close in on the molecules directly required for the E2F4 control of red blood cell production. Because defects in the E2F family of proteins or the proteins that regulate them, the retinoblastoma, pRB family, have been implicated as central for cancer development, these studies will have broad implications for therapeutic targeting of this pathway in cancer.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $447,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cell Development (Incl. Cell Division And Apoptosis)

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Cancer | E2F | Erythroleukaemia | Macrocytic Anemia | cell biology | cell cycle | erythropoiesis | transcription

Related Links