DNA methylation is a key epigenetic mechanism that involves addition of a methyl group to the cytosine of a CpG dinucleotide in DNA. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. Methylation of DNA is required for proper gene regulation during development and is involved in X-chromosome inactivation and allele-specific silencing of imprinted genes. It also plays a crucial role in the development of nearly all types of cancer.
Histone methylation is a process by which methyl groups are transferred to amino acids of histone proteins. Methylation of histones can either increase or decrease transcription of genes, depending on which amino acids in the histones are methylated, and how many methyl groups are attached. Methylation events that weaken chemical attractions between histone tails and DNA increase transcription. This is because they enable the DNA to uncoil from nucleosomes so that transcription factors and RNA polymerase can access the DNA. This process is critical for the regulation of gene expression that allows different cells to express different genes.
Acetylation and deacetylation of the lysine residues within the N-terminal tail protruding from the histone core of the nucleosome are essential processes of gene regulation. These reactions are typically catalysed by enzymes with histone acetyltransferase (HAT) or histone deacetylase (HDAC) activity.
Acetylated histones represent a type of epigenetic marker within chromatin. Acetylation removes the positive charge on the histones, thereby decreasing the interaction of the N termini of histones with the negatively charged phosphate groups of DNA. As a consequence, the condensed chromatin is transformed into a more relaxed structure that is associated with greater levels of gene transcription. This relaxation can be reversed by HDAC activity. Relaxed, transcriptionally active DNA is referred to as euchromatin. More condensed (tightly packed) DNA is referred to as heterochromatin.
Bromodomains are protein domains, found in many proteins associated with transcription and chromatin that recognise acetylated lysine residues. Bromodomains, as the “readers” of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. This recognition is often a prerequisite for protein-histone association and chromatin remodelling, making them important in epigenetics research.