Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 118-124).

Thesis (Ph. D.)--Illinois State University, 2005. / Title from title page screen, viewed September 26, 2006. Dissertation Committee: Kevin Edwards (chair), David Borst, Laura Vogel, David Rubin, Jon Friesen. Includes bibliographical references (leaves 133-143) and abstract. Also available in print.

Thesis (M.Sc.)--York University, 2005. Graduate Programme in Mathematics and Statistics. / Typescript. Includes bibliographical references (leaves 201-205). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss &rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR11838

Thesis (M.S.)--Montana State University--Bozeman, 2007. / Typescript. Chairperson, Graduate Committee: Tom Blake. Includes bibliographical references.

Genome wide association studies have shown that common variants in the human fat mass and obesity-associated (FTO) gene predispose to obesity and increased fat mass. Mice globally lacking Fto are lean, while mice globally overexpressing Fto have increased body weight due to increased fat mass. FTO protein was shown to localise to the nucleus and demethylate ssDNA and ssRNA. However, the mechanisms by which FTO mediates its effects on body phenotype remain unknown. In this thesis, I found that native FTO can be detected in both the nucleus and the cytoplasm during interphase, and that nuclear FTO was exported through the nuclear membrane during early prophase of the mitotic cell division. I developed co-immunoprecipitation (Co-IP) protocol to pull-down native FTO and identified a large number of new candidate binding partners (CBPs). Computational analysis predicted a role for FTO, and many CBPs, in RNA post-transcriptional modification and processing. I confirmed that the E3 ubiquitin-protein ligase TRIM21 interacts with FTO in multiple mouse tissues and binds FTO through its SPRY domain. Importantly, TRIM21 ubiquitinated FTO which did not lead to its degradation. FTO partially co-localised with TRIM21 and the decapping enzyme DCP2 in mRNA processing bodies (p-bodies). Overexpression of TRIM21 led to the accumulation of FTO outside the nucleus, but was reversed when both proteins were overexpressed. Additionally, I created a muscle specific Fto knock-out mouse model and found that lack of FTO in muscle did not result in the body composition phenotype reported in global Fto knock-out mice. Taken together, FTO can function in both the cytoplasm and the nucleus, where it interacts with TRIM21 which ubiquitinates FTO and potentiates its cytoplasmic localisation. Moreover, function of FTO in muscle does not mediate the obesity phenotype in mice.

Philosophiae Doctor - PhD / The pattern of inactivation in the DXS8237E-UBE1-PCTK1 region is of particular interest, since the mechanisms of X chromosome inactivation and the escape from inactivation are, as yet, not fully understood. The inactivation status of the DXS8237E and PCTKl gene differ: the first undergoes normal inactivation and the second escapes this process. The status of the UBEl gene has been controversial, although it is widely excepted that it does escape X chromosome inactivation. Physical mapping of the region employing YACs and subsequently P ACs has been undertaken, but was restricted in scope by the high frequency of rearrangements occurring. DNA sequences between DXS8237E, UBE1, PCTKl and the distal gene, UHX1, have been investigated with regard to LINEI elements, which are thought to playa role in X-inactivation. The results obtained strongly suggest a link between LINE1 elements and X chromosome inactivation. Sequence analysis results also contributed to the understanding of difficulties with restriction mapping of the region. Further, this work includes the first reported establishment of the UBEl exonintron boundaries. Additionally, genomic sequence analysis showed that only 46kb separate DXS8237E from UHX1, which confirms that this region is extremely gene rich. / South Africa

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Thesis (Ph.D.)--University of Melbourne, Howard Florey Institute and Dept. of Biochemistry and Molecular Biology, 2006. / Typescript. Includes bibliographical references (leaves 133-150).