The ability of stem cells to generate different types of tissue is rooted in their ability to regulate gene expression according to their environment (epigenetic regulation). Thus the therapeutic properties of stem cells are intimately related to how genes are expressed, which in turn is controlled by how the DNA-containing chromatin is organized within the nucleus. In particular, the ability of transcription factors to access specific regions of DNA is believed to be affected by local fluctuations in chromatin structure that occurs via chemical events like nucleosome sliding. We are interested in the basic chemical events which underlie the very complicated biological process of gene expression.
Our work is basically biophysics, and centers on using novel, high-spatial resolution fluorescence microscopy techniques to directly measure the spatial motion of chromatin in cells and biological systems. By varying ionic strength and crosslinking within isolated nuclei and XTC-2 cells, we have shown that fluctuations that occur on the 100 nm length scale, detectable in a fluorescence microscope, are consistent with the presence of core histone motion along the DNA. This work provides a window into the level of chromatin activity inside functioning cell nuclei, and is the first step in developing a general fluorescence based assay for transcriptional activity in live cell nuclei. In terms of stem cells, one ultimate goal would be to use fluorescence techniques to determine how stem cells activate local chromatin regions in the nuclei of cells that comprise growing tissue.
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