Butyrate is a short chained fatty acid that induces histone hyperacetylation by inhibiting histone deacetylases. This hyperacetylation of histones then leads to a change in chromatin conformation and transcription of genes. Histone deacetylases have recently been found to directly affect gene expression by associating with transcriptional repressor complexes. The present thesis describes the initial characterization of histone deacetylase activity in variants of HeLa cells that are capable of growth in cytotoxic concentrations of butyrate. Analysis of acetylation levels of total histones by triton-acid-urea gels indicated that the histone deacetylases in the variants are less sensitive to the effects of histone deacetylase inhibitors than the parental HeLa cells. Control experiments showed that this resistance was not due to the transport of butyrate into the cell nor from the overexpression of HDAC1 or HDAC2, further suggesting that the resistance to butyrate is due to an alteration in a gene encoding HDAC.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30361 |
| Date | January 1999 |
| Creators | Crosato, Milena. |
| Contributors | Th'ng, John P. H. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001740520, proquestno: MQ64337, Theses scanned by UMI/ProQuest. |
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