|Department:||Molecular Biology and Biochemistry|
|Keywords:||Epigenetics; Metabolism; sirtuins; Histones; Chromatin-modifying enzymes; Glyceraldehyde 3-phosphate dehydrogenase|
|Full text PDF:||http://wesscholar.wesleyan.edu/etd_diss/37|
Cells are constantly changing their metabolic status in response to extracellular signaling and availability of nutrients. These adjustments involve distinct transcriptional responses that reflect the redirection of biological efforts to return cells to homeostasis. The associated transcriptional profiles are characterized by unique states of chromatin structure. Chromatin-modifying enzymes, which are responsible for regulating particular chromatin structure states, require cofactors that are intermediates of cell metabolism. This presents a possible link for how the metabolic state of a cell is integrated into the regulation of the histone modifications resulting in the expression of certain sets of genes. It is possible that metabolic flux or enzymes that sense metabolite intermediates may influence the activities of chromatin-modifying enzymes and, therefore, chromatin structure. This merging logic has guided recent research efforts to focus on the potential links between metabolic enzymes and chromatin-modifying enzymes. In particular, this work focuses on characterizing a link between an NAD<sup>+</sup>-dependent histone deacetylase enzyme Sir2 and the glycolytic enzyme GAPDH (glyceraldehyde 3-phosphate dehydrogenase), in Saccharomyces cerevisiae cells.