Date of Graduation
Eberly College of Arts and Sciences
Karen S Weiler
The organization of eukaryotic genomes requires a harmony between efficient compaction and accessibility. This is achieved through the packaging of chromatin and the influence of chromosomal proteins, a topic not well understood. A chromosomal protein that remains a mystery at present is the D1 protein. Identified in 1974 by Alfageme et al., D1 has been highly characterized but its function remains unknown. The goal of this study was to elucidate the function of D1 by overexpression analysis using the GAL4/UAS system in Drosophila melanogaster. Analysis of gain-of-function phenotypes due to D1 overexpression in a variety of tissues determined that ectopic D1 interfered in the genetic cascades of a number of unrelated processes and in unrelated tissues. In addition, ectopic expression of D1 in the salivary glands led to ectopic associations of the polytene chromosomes resulting in chromosome entanglement. Mapping of the cytological intervals of these ectopic contacts resulted in a strong correlation to the localization of features of intercalary heterochromatin. An additional study indicated that D1 is activated by interaction with protein kinase CK2. I hypothesize overall, based on this study that the phosphoprotein D1, activated by protein kinase CK2, has a role in inducing and/or maintaining heterochromatic properties of the genome by binding to AT-rich satellite and satellite-related DNA in a variety of processes and tissues. The D1 protein, with ten copies of the AT hook binding motif, most likely functions in tandem with other transcription factors as a means of facilitating structural changes to chromatin resulting in the regulation of gene expression.;The D1 protein binds to the 1.688 g/cm3 and 1.672 g/cm 3 satellite repeats of heterochromatin as well as several euchromatic loci. Analysis of D1 cDNA determined the presence of ten copies of the highly conserved AT hook binding motif, a motif hypothesized to participate in facilitating architectural changes in the DNA. D1 mRNA is maternally loaded and highly expressed at the beginning of embryonic development and later in adult gametogenesis. In addition, the D1 protein has been compared to proteins of the mammalian High Mobility Group A family (HMGA), proteins functioning as architectural elements that alter the structure of DNA to produce and enhance various DNA-dependent activities. Even though D1 has been highly studied, its function remains unknown. Elucidating the function of the D1 chromosomal protein may provide intriguing information of the relationship between chromatin structure, gene expression and gene regulation, an understanding that once fully elucidated would revolutionize many fields.
Smith, Marissa B., "Using gain of function genetics to explore the role of non-histone chromosomal protein D1 in Drosophila melanogaster" (2007). Graduate Theses, Dissertations, and Problem Reports. 4338.