published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Marked by a defect in the production of the Beta (β)-globin chain that make-up hemoglobin, Beta (β)-thalassemia is the most prevalent form of inherited single-gene disorders in the world. To understand the molecular mechanisms that govern the expression of the β-globin polypeptide encoded by the β-globin locus, we examined closely the enzymes involved in the epigenetic regulation of gene expression through histone 3 lysine 9 mono and di-methylation (H3K9 me1/2). G9a-like protein (GLP), a mammalian methyltransferase involved in the establishment and maintenance of H3K9 me1/2 mark at euchromatin, regions was found to be critical for the full activation of the adult β-globin genes in vivo during Murine erythroleukemia cell line (MEL) differentiation. Though it was initially hypothesized that GLP binding to H3K9 me1/2 mark through its Ankyrin domain was key to its activating function, we found that Flag- GLP ankyrin mutants E817R and W791A unable to bind to the methyl mark, are able to activate β-globin genes as well as their wild-type counterpart. Additionally, this study found that the embryonic gene εγ, known to be re-activated after G9a KD at the mRNA level, was effectively transcribed at the protein level using Triton Urea Acetic acid (TAU) western blots, thereby identifying potential therapeutic applications for treatment for β-thalassemia patients.

Erratum pasted on front fly-leaf. / Bibliography: leaves 180-202. / xvii, 220 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The evolutionary relationships of the beta-like globin genes were studied by applying maximum parsimony methods to aligned DNA sequences. / Thesis (Ph.D.)--University of Adelaide, Dept. of Genetics, 1998?

"January 2003" / Addendum on back page. / Bibliography: p. 175-184. / 184 p. : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / "In the study reported in this thesis, a PCR-based approach was used to isolate the b-like globin genes that are present in the tammar wallaby, Macropus eugenii, including the gene that encodes the w-globin chain. Three -like globin genes (b-, e-, w-) that had previously been described at the protein level in the tammar wallaby were characterised. w-globin orthologues were also identified in a wide range of marsupial species, and in one of these species, the dunnart (Sminthopsis crassicaudata), the complete DNA sequence of the w-globin gene was determined. Southern analysis in the dunnart and in situ hybridisation in the tammar wallaby, provided evidence for the unexpected conclusion that w-globin is not part of the -globin gene cluster in these species. RT-PCR studies using RNA isolated from a new-born dunnarts confirmed that w-globin is expressed in this species. Therefore, this is the first report of an "orphaned" b-like globin gene that is expressed in a vertebrate." --p. 6. / Thesis (Ph.D.)--University of Adelaide, Dept. of Molecular Biosciences, 2003

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available online.

Thesis (Ph. D.)--University of Adelaide, Dept. of Genetics, 1992. / Includes bibliographical references (leaves 212-235).

Thesis (Ph. D.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 243-274).

Thesis (Ph. D.)--University of Hong Kong, 1997. / Includes bibliographical references (leaves 121-153).

Thesis (Ph.D.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 243-274). Also available in print.

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.