Reading the Blueprint
Eukaryotic gene expression is regulated at the DNA, RNA, and protein level. The process of gene regulation at the DNA level is referred to as epigenetics. Epigenetics is the study of heritable changes in gene expression that do not involve alterations of the DNA sequence (Kelly et al., 2010). Many of these changes involve alterations of the chromatin: the state in which DNA is stored inside the cell. Eukaryotic DNA is packaged in nucleosomes, which comprise octamers of four core histone proteins (H2A, H2B, H3 and H4) around which 147 bp of DNA is wrapped. Accessibility of DNA is determined by repositioning and restructuring of the nucleosomes by ATP-dependent chromatin remodellers, through covalent modifications of the histones by histone-modifying enzymes and through modifications on the DNA itself by DNA-modifying enzymes. There is substantial interplay between the many epigenetic regulators, which together control transcription. Globally, chromatin can be in two states, the open state (euchromatin) in which DNA is available for transcription and a closed state (heterochromatin) in which the DNA is tightly packed, precluding its transcription.