Embryonic development requires the precise regulation of gene transcription at the levels of both tissue and temporal specificity. While it has long been appreciated that transcription factors are necessary for regulating this specificity it is becoming increasingly clear that transcription factors alone are not sufficient to control gene expression. One other issue critical to the control of gene expression is the structure of chromatin. ATP-dependent chromatin remodeling factors are capable of shifting the position of or entirely removing proteins bound to DMAthat would otherwise block the access of transcriptional machinery. The goal of this project is to examine the function of the PBAF (Polybromo Associated Fatctor) specific SWI/SNF chromatin remodeling complex subunit BAF200 in mouse embryonic development to begin to elucidated the importance of this subunit in vivo. Furthermore, evidence I have collected suggests that SWI/SNF mediated chromatin remodeling is specifically required for the process of blood vessel angiogenesis. Therefore I propose experiments to specifically inactivate BAF200 in endothelial cells to determine if it is PBAF ? iy,;;: mediated chromatin remodeling that is responsible for SWI/SNF contribution to vascular development: In' addition, I propose experiments to look for genes whose expression is specifically controlled by complexes containing BAF200, using complementary approaches in the mouse yolk sac and in an endothelial cell culture model. Hopefully these approaches will allow me to identify novel genes involved in the development of the vascular system or to further the understanding of how known players in vascular development are transcriptionally regulated. Because diseases of the vasculature affect so many people in the world, understanding the genes and processes involved in blood vessel development is vital. By investigating the role of chromatin remodeling factors in endothelial cells we may identify novel genes whose expression is important to blood vessel function and that are regulated by chromatin architecture. Such genes, and perhaps the chromatin remodeling factors themselves, may turn out to be effective targets for treating diseases in which blood vessels are affected, including such diseases as coronary artery disease, diabetes and cancer.
