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.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains vii, 82 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 60-82).

Thesis (M.S.)--California Polytechnic State University, 2010. / Title from PDF title page; viewed on May 15, 2010. Major professor: Scott Hazelwood, Ph.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Engineering, with a Specialization in Biomedical Engineering." "April 2010." Includes bibliographical references (p. 73-78).

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2005. / Vita. Appendix A: "C program listing." Includes bibliographical references (leaves 201-211).

Chromatin remodelers are ATP-dependent multisubunit assemblies that regulate transcription and other processes by altering DNA-histone contacts. The mechanism of action is based on the transduction of energy released by ATP hydrolysis to translocation on DNA and ultimately the movement of histones in cis or trans. Though the critical ATP burning and translocation activities are fulfilled by a conserved ATPase domain in the catalytic subunit, there are accessory domains and subunits that are speculated to regulate these activities. Important questions in the field center around the identification of these domains and subunits, whether they affect complex formation, substrate affinity or a critical step in remodeling. If they do affect remodeling, what is the structural basis of the regulatory activity. In this study, these questions have been addressed using the prototype remodeler SWI/SNF from budding yeast. ySWI/SNF is a 12 subunit complex that includes the catalytic subunit Swi2/Snf2. It affects 6% of the yeast genome being primarily involved in gene activation. We employed a systematic protein or domain deletion strategy and characterized the mutant complexes in vitro and in vivo. A key finding was that SWI/SNF is organized in distinct structural modules and that the Snf2 module regulates most of its activities. Snf2 is a central subunit in this module and the function of conserved regions within Snf2 were studied. The N terminus preceding the HSA and ATPase domain has three major roles - complex assembly, recruitment and regulation of catalytic activity. A novel SnAC domain located C terminal to ATPase domain was identified to play critical role in coupling ATP hydrolysis to nucleosome movement by acting as a histone anchor. Finally the tandem AT-hooks between SnAC and bromodomain serve as DNA binding domains but also affect ATPase activity and nucleosome mobilization independent of its binding activity. Taken together, this study provides a comprehensive overview of the function of regulatory domains in SWI/SNF.

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.

No description available.

INO80, a member of the multi-subunit SWI2/SNF2 superfamily, is involved in transcription regulation, DNA repair and replication. Not much is known about its substrate specificity and remodeling mechanism or how it differs in comparison to SWI/SNF or ISWI. Site-directed mapping of histone-DNA contacts showed that INO80 generally remodels mononucleosomes by moving them to the center of DNA. The length of extranucleosomal DNA was found to play an important role in nucleosome binding as well as remodeling by INO80 much like ISW2 and ISW1a. INO80 preferentially binds to nucleosomes containing >20bp of extranucleosomal DNA. Similarly, INO80 remodeling of mononucleosomes with different lengths of extranucleosomal DNA showed that at least 33bp of extranucleosomal DNA on one side of the nucleosome was required for initiation of remodeling. These data suggest that INO80 behaves much like ISW2 and ISW1a complexes based on their requirement for extranucleosomal DNA. INO80 does not unravel or displace nucleosomes like SWI/SNF. There are several key aspects of how INO80 interacts with and remodels nucleosomes that are quite distinct from SWI/SNF, ISW2, and ISW1a. Previously SWI/SNF and ISW2 were shown to initiate nucleosome movement by translocating along nucleosomal DNA two helical turns from the dyad axis. Nucleosome movement by INO80 instead requires translocation by the complex along nucleosomal DNA near the entry/exit site at the dimer-tetramer interface. Sliding interference of INO80 by the presence of nicks indicated that torsional strain at the site of translocation is required for nucleosome mobilization by INO80. Hydroxyl radical footprinting of the INO80-nucleosome complex shows found that INO80 interactioninteracts with extranucleosomal DNA at, the entry-exit site and to lesser extent at the dyad axis, but it lacks the protection found indoes not contact 2 helical turns from the dyad like ISW2 and SWI/SNF at two helical turns from the dyad axis as determined by photoaffinity cross-linking studies. The catalytic subunit (Ino80) rather than being found associated 2 helical turns from the dyad, was bound to extranucleosomal DNA and nucleosomal DNA near the entry-exit site. Other subunits (Arp8p, Arp5p and Nhp10) were also found to be contacting both nucleosomal and extranucleosomal DNA. Site-specific histone cross-linking studies revealed that Ino80, Arp5 and Arp4 interact extensively with the histone dimer of the nucleosome in comparison to H3-H4 tetramer. Although N-terminal histone tails are often important for chromatin remodeling, INO80 shows no requirement of histone tails for its nucleosome binding and mobilizing activities. The deviation of INO80 from the canonical model of how ATP-dependent remodelers interact and mobilize nucleosome is apparently due to its unique role as a member of the remodeling complexes that promote the exchange of H2A/H2B dimer from core nucleosome particle.

Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Includes bibliographical references (p. 131-133). / This thesis deals with inhabitants' modifications of the 19th century sidehall houses in East Boston, now a predominantly Italian neighborhood. On the basis of the data obtained by a survey and observations, the practical reasons and social and psychological implications of each identified pattern of both interior and exterior modification are analyzed. Inhabitant s modify their houses according to their changing living situations, or special needs that are different in each family. They can correspond with the changing living standard in the whole society and developing technology by constantly modifying their houses. Housing modification functions as an important adaptation mechanism especially for working class people who cannot easily move from one place to another because of financial constraints and the tight social relationships among them in the region. Modifications are also a means of self-expression for the inhabitants. As they modify their houses they always try to imply their taste and values through the modifications. They try to define their own territories and personalize them through modifications. Modifications are the results of inhabitants' active reactions to such needs, which are quite essential to them. After all, home modification, which has been ignored by most architects despite its familiarity in the United States, has great significance to the inhabitants, psychologically as well as practically. It enhances the inhabitants' sense of ownership, competence and self-worth. / by Toshihito Yokouchi. / M.Arch.