Date of Graduation

Summer 2011

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Joshua Smith

Keywords

histone, deacetylase, Tetrahymena, HDAC11, THD5, epigenetics

Subject Categories

Medical Molecular Biology

Abstract

The packaging of chromatin plays a large role in the ability of genes to either be accessible (euchromatin) or inaccessible (heterochromatin) to transcription factors. In order for changes to occur in the chromatin state, histone proteins in the nucleosomes are modified (acetylation, methylation, phosphorylation, etc). Histone acetyltransferase (HAT) and histone deacetylase (HDAC) add or remove acetyl moieties from the histone proteins, respectively, to maintain the dynamic chromatin states. HDACs are difficult to study due to the fact that many processes such as transcription, mitosis, and silencing of genes are all occurring in the nucleus simultaneously. Tetrahymena thermophila, with its two distinct nuclei make it an ideal model organism for studying the functions of HDACs. A homolog of HDAC11 has been identified in T. thermophila (T. thermophila histone deacetylase 5; THD5). THD5 is the first class IV HDAC identified in a unicellular eukaryote, and ciliates are the only unicellular eukaryote to have HDAC11 homologs. The purpose of this study was to provide initial characterization of THD5. The THD5 sequence was determined to contain two exons flanking a single intron Tagging THD5 with Green Fluorescence Protein (GFP) revealed a cytoplasmic localization. THD5 was found to be maximally expressed during 7 and 10 hours of conjugation (macronuclear differentiation and degradation) and around the end of macronuclear division in the cell cycle. THD5 was knocked down and mutants showed a defect in macronuclear division. These results indicate that THD5 may have a role in macronuclear division. It remains unclear if this deacetylase functions by changing the modification state of histones or other proteins such as microtubules.

Copyright

© Steven Craig Snyder

Campus Only

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