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Actin polymerization in gene expression

Posted on:2003-01-03Degree:Ph.DType:Dissertation
University:Stanford UniversityCandidate:Rando, Oliver JoaquinFull Text:PDF
GTID:1460390011978216Subject:Biophysics
Abstract/Summary:
In order to better understand the mechanism of action of Swi/Snf-like chromatin remodeling complexes, we investigated the role of actin and the actin-related BAF53 in the human Swi/Snf-like BAF complex. Here, we present evidence that actin and BAF53 are involved in targeting of the BAF complex to the nuclear scaffold. We show that this scaffold association can be regulated by a number of signaling mediators, including the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). We further show that binding of PIP 2 to the BAF complex allows the BAF complex to stabilize actin filaments by binding to filament ends and filament branch points, and suggest a mechanism for this regulation. In order to identify potential target genes of BAF function in vivo, we used cDNA microarrays to interrogate gene expression changes in peripheral T-cells and in the Jurkat T-cell line under a variety of conditions. We identify genes whose activation in Jurkats requires both actin polymerization as well as an intact BAF complex. In addition, we present results of studies on gene expression in T-cells in response to activation and in response to perturbations in the cytoskeleton.
Keywords/Search Tags:Actin, BAF complex, Gene
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