Chapter 6 - DNA Methylation Analysis: Providing New Insight into Human Disease

Abstract

The human genome contains four bases—guanine, adenine, thymine, and cytosine. The cytosines can be either methylated or unmethylated at the fifth carbon position in the pyrimidine ring. In general, they can only be methylated when they are in the context of a CpG dinucleotide that involves a cytosine immediately followed by a guanine. The methylation status of a CpG island is correlated with the chromatin structure and expression levels of nearby genes. CpG islands associated with actively transcribed genes are typically unmethylated. When a CpG island is methylated, methyl-CpG-binding domain proteins recognize the methylated CpG and recruit the necessary factors for chromatin condensation and gene inactivation. This DNA methylation state is maintained during cell division by a family of enzymes called DNA methyltransferases. Cancer was viewed as an accumulation of chromosomal aberrations and, therefore, called a “genetic disease.” However, it has become clear over time that epigenetic changes play a crucial role in carcinogenesis. While attention is focused on methylation in carcinogenesis, a similar groundswell of research is emerging on methylation in other diseases, especially autoimmune and cardiovascular conditions.