Chromatin remodelers such as CHD1 (chromodomain, helicase/ATPase, DNA-binding domain) regulates histone dynamics and allows for higher order of chromatin compaction.CHD1 has been found to be important in fertility, wing development, and it colocalizes with elongating RNA polymerase II in Drosophila melanogaster. CHD1 is also important in embryonic stem cell pluripotency in mice and chd1 is the second most deleted gene in prostate cancer in humans. Furthermore, CHD1 suppresses the level of H3 dimethylated on lysine 9 (H3K9me2) and heterochromatin protein 1a (HP1a) to antagonize repressive chromatin. To complement these studies, I am seeking to determine the possible role of CHD1 on H3K9me2 and H3K56ac. Influence of CHD1 on histone dynamics is examined by using native chromatin immunoprecipitation at CrebA. We observed that H3K9me2 levels do not significantly increase over a single active gene in Drosophila salivary glands with the loss of CHD1, which implies CHD1’s effect might be only limited to heterochromatic regions. Additionally, I have preliminary evidence that the loss of CHD1 leads to an increase in the level of H3 acetylated on lysine 56, a mark of newly deposited histones. This evidence together with yeast studies provides a model for how CHD1 regulates nucleosome turnover.

No description available.

Folliculogenesis is a complex process which describes the maturation of the ovarian follicle, from the primordial stage all the way to the ovulation of the antral follicle, and its sequela, the formation of the corpus luteum (CL). Imitation switch (ISWI) proteins are a class of ATP-dependent chromatin remodelers which mobilize nucleosomes to regulate a number of cellular processes including transcription, replication, and DNA repair. The pattern of expression of the mammalian ISWI proteins SNF2H and SNF2L in the mouse ovary suggests a role in the coordination of the proliferation and differentiation of granulosa cells during folliculogenesis. Here, we report that SNF2H is associated with proliferating granulosa cells, while SNF2L expression is induced following the LH surge which triggers their terminal differentiation into luteal cells. Knockdown of Snf2l by siRNA is sufficient to downregulate the expression of StAR, an important steroidogenic enzyme, and marker of the CL. Furthermore, SNF2L is thought to directly regulate StAR expression by physically binding to its promoter as indicated by chromatin immunoprecipitation (ChIP). In order to identify additional targets regulated by SNF2L, an unbiased microarray screen was developed to look for genes induced by LH in a SNF2L-dependent manner. One of the candidates, Fgl2 is strongly induced at 8h post hCG only in granulosa cells with intact SNF2L activity. Furthermore overexpression of SNF2L is sufficient to induce FGL2, and SNF2L is present on its promoter in the SIGC rat granulosa cell line. Some of the SNF2L binding partners that may be important in this regulation are PR-A and FLI-I, which have been found to interact with SNF2L by IP. Finally we describe here the phenotype of a Snf2l KO mouse which includes multiple reproductive defects, including resistance to superovulation, low secondary follicle counts, and a high incidence of abnormal antral follicles. Taken together these data suggest an important role of ISWI proteins in folliculogenesis, particularly SNF2L, which may regulate multiple genes important for the terminal differentiation of granulosa cells into luteal cells following the LH surge.

Thesis (M.S.)--Michigan State University. Dept. of Biochemistry and Molecular Biology, 2006. / Title from PDF t.p. (viewed on Nov. 20, 2008) Includes bibliographical references (p. 100-101). Also issued in print.

Thesis (Ph. D.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on June 17, 2009) Vita. Includes bibliographical references.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1988. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph.D)--Biology, Georgia Institute of Technology, 2009. / Committee Chair: Marion B. Sewer; Committee Member: Alfred H. Merrill, Jr.; Committee Member: Donald F. Doyle; Committee Member: Dr. Edward T. Morgan; Committee Member: Kirill S. Lobachev. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Universiẗat, Diss., 2005--Würzburg.

Tierärztliche Hochsch., Diss., 2005--Hannover.

Thesis (Ph. D.)--Lehigh University, 2000. / Includes vita. Includes bibliographical references (leaves 151-159).