Roles of DNA and histone methyltransferases during zebrafish development

The research work presented in this dissertation describes the roles of the major DNA methyltransferases and histone methyltransferases in zebrafish development. DNA and historic methylation are two key processes that regulate transcription of genes in mammals. Both of these processes are essential for proper development of an organism and their misregulation leads to multiple diseases including cancer. A better understanding of these two processes will help us understand how an organism develops and will also help in designing more effective drugs against cancer. Chapter 1 is an introduction on DNA and histone methylation and the enzymes which catalyze these processes. This chapter summarizes the literature on the normal status of DNA methylation in somatic cells, its dynamics during early development of various organisms including zebrafish, how abnormalities in this process lead to cancer, the protein structure and function of the known DNA methyltransferases and findings about relationship between histone methylation and DNA methylation. Chapter 2 describes the function of DNA methyltransferase-1 during zebrafish development. The focus of the studies described in this chapter is on the function of this enzyme during later differentiation during tissue-specific development. Also, the epistatic relationship between Dnmt1 and Suv39h1, the major H3K9 methyltransferase, is described in this chapter. Chapter 3 shows our findings about role of Dnmt3, a member of other sub-class of DNA methyltransferase family, during zebrafish development. Here I have shown novel roles of this enzyme during development of vertebrate brain. In Chapter 4, I have described our novel findings regarding the role of Dnmt2, a mysterious DNA/RNA methyltransferase, during zebrafish development. Here, I have also described the importance of its function in the cytoplasm. Chapter 5 is an attempt to compare the phenotypes obtained by knocking-down protein levels of different DNA methyltransferases. This chapter is the crux of our studies which shows striking similarities and differences of in vivo functions of different classes of DNA methyltransferases. In Chapter 6, the main conclusions of my work are summarized. I have also discussed the implications of our findings and the future approaches to unravel the mysteries of developmental functions of DNA methyltransferases.