Stevie Lynne Kohler

Alaska INBRE Undergraduate Research Fellow, summer-fall 2009, and summer 2010
Genes exist within the context of chromatin, a complex of DNA and protein that compacts DNA into the eukaryotic nucleus. In addition to limiting the space that DNA takes up, this compaction also serves to regulate gene expression, since genes must be physically accessible to allow for transcription. Proper neural development requires a complex set of regulatory events that ensure the expression of particular genes at precise spatial and temporal points. In order to allow access at these points, chromatin remodelers must alter chromatin structure around the genes in question. Williams Syndrome is a neurodevelopmental disorder, characterized by mental retardation and aberrant visual processing, which is caused by a deletion on chromosome 7. This deletion includes the Williams Syndrome Transcription Factor (WSTF), which is known to dimerize with Imitation Switch (ISWI) to form the ATP-dependent chromatin remodeling complex WICH in Xenopus laevis. The mammalian chromatin remodeling complexes WINAC and B-WICH have previously been shown to include WSTF, and homologs of these complexes may exist in Xenopus embryos. Vitamin D Receptor (VDR), which is stably associated with mammalian WINAC, is present in Xenopus. I am investigating whether there are Xenopus homologs of mammalian WINAC and B-WICH complexes. Additionally, I am determining whether WSTF knockdown affects VDR-responsive genes and whether this impacts calcium metabolism, which is known to be perturbed in Williams Syndrome.