Heterochromatin: silence is golden

The large genomes of higher eukaryotes suggest a need for stable packaging, particularly as most of the DNA does not code for proteins, and much consists of repetitious sequences, including remnants of invading retrotransposons, transposable elements and the like. Cytological studies first demonstrated that much of the repetitous DNA is packaged in a condensed form referred to as heterochromatin, and indicated that such packaging limits transcription. During the last few years, remarkable progress has been made in identifying the biochemical characteristics of heterochromatin, suggesting mechanisms by which heterochromatin formation is targeted and maintained. Biochemical marks of heterochromatin An important characteristic of heterochromatin is that this mode of packaging is epigenetically inherited; i.e. the packaging state is generally maintained after replication and mitosis, independent of the underlying DNA sequence. This implies a biochemical mark and a cellular machinery that can recognize and maintain the mark locally. The DNA of eukaryotic genomes is packaged in nucleosomes, with around 167 base pairs (bp) of DNA wrapped in two left-handed turns around a core of eight histones (an [H3+H4] 2 tetramer and two dimers of [H2A+H2B]). Histone H1 binds to the DNA where the DNA enters and exits from association with the core. 'Linker' DNA of around 10–50 bp extends to the next histone core. The carboxy-terminal two thirds of the core histones establish the very stable interactions that create the octamer and bind DNA to its surface, whereas the amino-terminal tails are available for interaction with other chromosomal components. The tails are substrates for a number of enzymes that modify specific amino acids of specific histones. While general patterns had been noted, the significance of these histone modifications was first recognized with the demonstration that a particular histone acetyltransferase was the product of a gene previously identified as an activator of gene expression. Heterochromatin is characterized by histone hypoacetylation (in all eukaryotes) and by methylation of histone H3 on lysine 9 in higher eukaryotes, but not in some single-celled eukaryotes such as Saccharomyces. Histone H3 methylated at lysine 9 (H3-mK9) is bound by Heterochromatin Protein 1 (HP1), a highly conserved protein that is directly associated with pericentric heterochromatin. 'Constitutive heterochromatin', which is commonly found around centromeres and telomeres, displays the same condensed packaging in all somatic cell types of an organism (Table 1). 'Facultative heterochromatin' refers to regions of the chromosome that appear densely packaged and have lost gene expression, in which the …