Browsing by Subject "promoter"
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Item Chromatin dynamics at the Saccharomyces cerevisiae PHO5 promoter(Texas A&M University, 2006-04-12) Jessen, Walter JosephIn eukaryotes, the organization of DNA into chromatin is a primary determinant of gene expression. Positioned nucleosomes in promoter regions are frequently found to regulate gene expression by obstructing the accessibility of cis-regulatory elements in DNA to trans-factors. This dissertation focuses on the chromatin structure and remodeling program at the S. cerevisiae PHO5 promoter, extending the use of DNA methyltransferases as in vivo probes of chromatin structure. Our studies address the diversity of histone-DNA interactions in vivo by examining nucleosome conformational stabilities at the PHO5 promoter. We present high-resolution chromatin structural mapping of the promoter, required to relate in vivo site accessibility to nucleosome stability and show that the PHO5 promoter nucleosomes have different accessibilities. We show a correlation between DNA curvature and nucleosome positioning, which is consistent with the observed differences in accessibility/stability. Kinetic analyses of the chromatin remodeling program at PHO5 show that nucleosomes proximal to the enhancer are disrupted preferentially and prior to those more distal, demonstrating bidirectional and finite propagation of chromatin remodeling from bound activators and providing a novel mechanism by which transactivation at a distance occurs.Item Combinatorial motif analysis in yeast gene promoters: the benefits of a biological consideration of motifs(Texas A&M University, 2005-02-17) Childs, KevinThere are three main categories of algorithms for identifying small transcription regulatory sequences in the promoters of genes, phylogenetic comparison, expectation maximization and combinatorial. For convenience, the combinatorial methods typically define motifs in terms of a canonical sequence and a set of sequences that have a small number of differences compared to the canonical sequence. Such motifs are referred to as (l, d)-motifs where l is the length of the motif and d indicates how many mismatches are allowed between an instance of the motif and the canonical motif sequence. There are limits to the complexity of the patterns of motifs that can be found by combinatorial methods. For some values of l and d, there will exist many sets of random words in a cluster of gene promoters that appear to form an (l, d)-motif. For these motifs, it will be impossible to distinguish biological motifs from randomly generated motifs. A better formalization of motifs is the (l, f, d)-motif that is derived from a biological consideration of motifs. The motivation for (l, f, d)-motifs comes from an examination of known transcription factor binding sites where typically a few positions in the motif are invariant. It is shown that there exist (l, f, d)-motifs that can be found in the promoters of gene clusters that would not be recognizable from random sequences if they were described as (l, d)-motifs. The inclusion of the f-value in the definition of motifs suggests that the sequence space that is occupied by a motif will consist of a several clusters of closely related sequences. An algorithm, CM, has been developed that identifies small sets of overabundant sequences in the promoters from a cluster of genes and then combines these simple sets of sequences to form complex (l, f, d)-motif models. A dataset from a yeast gene expression experiment is analyzed with CM. Known biological motifs and novel motifs are identified by CM. The performance of CM is compared to that of a popular expectation maximization algorithm, AlginACE, and to that from a simple combinatorial motif finding program.Item Role of Repressors in Fine Regulation of Development: Sxl and Its New Repressors Hey and Myc(2010-07-14) Kozhina, ElenaIn Drosophila, XX embryos express Sxl from the early promoter, SxlPe, and become females. At the same time, XY embryos with only one X chromosome become males. I investigated the role of repression in the establishment of the strict regulation of SxlPe. I found that the co-repressor Groucho, is responsible for amplification of the two-fold difference in X-encoded activator genes into an all-or-nothing difference in Sxl expression. Three new basic helix-loop-helix repressors of Sxl were identified: Hey, Cwo and the prooncogene Myc, all of which are maternally supplied. I have shown that Myc specific repression is important as early as cycle 10, which is 2 cycles earlier than the onset of normal Sxl expression.