| Complex organisms show a high degree of cellular specialization despite the fact that all cells share essentially the same genetic information. This structural and functional specialization is achieved through modulation of gene expression programs during development. Differences in expression patterns once established are maintained and enforced within each cell lineage, suggesting the presence of a mechanism allowing for a type of transcriptional memory. Epigenetic mechanisms which encode for an additional layer of biological information above the primary DNA sequence are now understood to contribute to this transcriptional memory (Bird, 2007). Additionally, through these critical modifications the cell is able to maintain genome stability and organization (Mohn and Schubeler, 2009).;At the molecular level, two distinct layers of epigenetic information can be distinguished. The first consists in the direct modification of the DNA through the covalent addition of methyl groups to cytosine bases, mostly in the context of CpG dinucleotides. The second layer, by contrast, consists in a diverse series of site-specific chemical modifications to the histone proteins around which nucleosomal DNA wraps (Klose and Bird, 2006; Kouzarides, 2007). Thus, all epigenetic information must be envisioned in the context of nucleosomes, the fundamental unit of chromatin. Understanding the exact processes by which epigenetic patterns are set and maintained during development in order to enforce cell-specific transcriptional programs and genomic integrity remains a major goal of current biology.;The body of work below will first introduce the role DNA methylation plays in epigenetic regulation and reveal what is known about the family of DNA methyltransferases responsible for the deposition of these epigenetic marks. The study I have undertaken, focusing on the biochemical characterization of the DNMT3B enzyme, the main de novo DNA methyltransferase, will then be presented. Finally, this work will discuss how these findings contribute to our understanding of DNMT3B function and epigenetic regulation. |
