Histone code hypothesis

The Histone Code is hypothesized to be a code consisting of covalent histone tail modifications. Together with other modifications as DNA methylation it is part of the epigenetic code.

The main role of histones is in associating with DNA to form nucleosomes, which themselves bundle to form chromatin fibers. They are globular proteins with a flexible N-terminus (taken to be the tail) that protrudes from the nucleosome. The chromatin structure plays an important role in regulation of gene expression, while the tail modifications play an important role in the chromatin structure. For details of gene expression regulation by histone modifications see table.

The Hypothesis
The hypothesis is that chromatin-DNA interactions are guided by combinations of histone modifications. While it is accepted that modulations (such as methylation, acetylation, ADP-ribosylation, ubiquitination and phosphorylation) to histone tails alter chromatin structure, a complete understanding of the precise mechanisms by which these alterations to histone tails influence DNA-histone interactions remains elusive. However, some specific examples have been worked out in detail. For example, phosphorylation of serine residues 10 and 28 on histone H3 is a marker for chromosomal condensation. Similarly, the combination of phosphorylation of serine residue 10 and acetylation of a lysine residue 14 on histone H3 is a tell-tale sign of active transcription.

Modifications
Possible modifications to the tails are: Deacetylation allows tight arrangement of chromatin, preventing gene expression, while acetylation may occur to open up the chromatin.
 * Acetylation - by HAT (Histone Acetyl Transferase); deactylation - by HDAC (Histone Deacetlyase)
 * Methylation
 * Phosphorylation
 * Ubiquitination
 * Ribosylation