Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation

Principal Investigator: Milena Stevanovic, PhD

SOX proteins constitute a large family of transcription factors implicated in regulation of various developmental processes. During nervous system development SOXB1 proteins (SOX1-3) control many different processes, including maintenance of pluripotency, specification and terminal differentiation. They continue to maintain neural progenitors in the adult brain, and controlling adult neurogenesis. SOX18 (SOXF member) is an important regulator of vascular development playing a role in endothelial cell specification, differentiation, normal and tumor angiogenesis. We will analyze the effects of Wnt and Sonic Hedgehog (SHH) signaling pathways on selected SOX genes expression and their impacts on neural differentiation and on angiogenic potential of endothelial cells. Further, we will study the involvement of epigenetic mechanisms, including DNA methylation, histone modifications and microRNA-mediated processes, in the control of SOX genes expression. Finally, we will study the effects of modulation of SOX genes expression on cell fate determination and differentiation. This proposal will bring together various approaches for studying mechanisms that control human SOX genes expression. Understanding transcriptional and epigenetic regulation of SOX genes expression, coupled with results obtained by gain- and loss-of-function studies, will enable further insight into the roles of these genes in control of differentiation and multiple developmental and physiological processes.


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