DNA Methylation and Gene Expression

Understanding the mechanisms involved in the regulation of gene expression in eukaryotic organisms is one of the major challenges facing the modern molecular biologist. Despite recent advances that permit the dissection of individual genes at the nucleotide level, the factors involved in the orchestration of gene activity during development are not well understood. Two general models usually are proposed for explaining differential gene expression. Since the genetic information seems to be faithfully inherited by every somatic cell and germ line, it has been suggested that chromatin conformation plays a role in the selective expression of individual genes in specific cell types. There certainly is a large body of evidence that convincingly shows that active gene regions have a unique chromosomal conformation characterized by a generally increased accessibility to a variety of DNA probes (Chapter 15). A second model that has been put forward raises the possibility that changes in the DNA methylation pattern of specific genes may be responsible for the observed tissue-specific gene expression. This article will provide some of the evidence that links DNA methylation to the regulation of gene activity and will attempt to probe the mechanism by which this modification may act to modulate gene expression in specific cell types.