REGULATION OF GENOMIC STRUCTURE AND TRANSCRIPTION IN DROSOPHILA

Abstract

Within the span of a single human lifetime, we have discovered that DNA is the basis of genetic inheritance, deciphered the genetic code, and determined the entire sequence of multiple human genomes. However, we still have only a basic understanding of many of the processes that regulate DNA structure, function, and dynamics. The work presented in this dissertation describes the roles of two sets of genes that regulate the expression of genetic information and its transmission from one generation to the next.The condensin II complex has been implicated in the maintenance of genomic integrity during cell division and in transcriptional regulation during interphase. These roles stem from its ability to regulate chromosome structure though the mechanisms of this regulation are unclear. Evidence suggests that it is important for chromosome condensation and segregation during mitosis and meiosis. We have shown that this complex regulates the condensation of chromosomes during interphase. Its ability to reduce chromosome axial length provides a mechanism for the establishment of chromosome territories. We have also shown that condensin II differentially regulates interactions between homologous and heterologous DNA sequences. These findings contribute to our understanding of the overall structure of the nucleus, the regulation of chromosome structure, and the regulation of gene expression.The function of the Drosophila gene, sticky, is poorly understood. It contributes to cytokinesis by phosphorylating myosin II, but it also has a role in the regulation of chromatin structure. Mutations in sticky are associated with a wide range of developmental abnormalities. We provide evidence that this gene regulates the expression of numerous other genes which contribute to the phenotypes observed when sticky is mutated. We also show that sticky function overlaps with that of dfmr1, an ortholog of the gene associated with the most common form of human mental retardation. These findings contribute to our understanding of transcriptional regulation in chromatin and its implications in development and disease.