Epigenetic Modifications Of Histones

The histone code is the summary of epigenetic

If you take a closer look at Histone, it is striking that they consist of a globular part with unstructured (outstretched) ends (N and C terminus). The globular regions of the histones form the nucleus of the nucleosome, which is wrapped in DNA. The unstructured ends on the contrary protrude from the nucleosome structure.

Histones can be chemically modified in unstructured and globular areas. These are epigenetic modifications. Over the last few decades, hundreds of histone modifications have been discovered, now grouped together in a so-called 'histone code'. The most studied modifications are acetylation (Ac), methylation (Me), phosphorylation (P) and ubiquitination (Ub).

Nomenclature

When describing histone modifications, a particular nomenclature is used.

It will be displayed:

(1) Which histone is modified (H2A, H2B, H3 or H4).

(2) The amino acid which is modified and its position within the histone protein (e.g., lysine 9, K9).

(3) The mode of modification (e.g., methylation - Me, acetylation -Ac, ubiquitinylation -Ub, etc.).

(4) The number of chemical groups attached. In many cases, one, two or even three identical chemical molecules can be attached to the amino acid. (eg me1, me2 or me3).

Examples:

H3K9me3 - Triple methylation of the lysine amino acid in the ninth position of the H3 histone protein.

H3K9ac - acetylation of the lysine amino acid in the ninth position of the H3 histone protein.

Effect of histone modifications on the genome

Histone modifications can affect the genome in two ways.

1. By inhibiting and promoting the attachment of factors

Different histone modifications may be connective plateaus for various regulatory factors. For example, H3K9ac and H3K4me3 may promote binding of 'activators' and inhibit 'inhibitors'. This leads to the 'opening' of the chromatin and gene activation. On the other hand, H3K27me3, H3K9me3 and H3K20me3 are examples of modifications that promote binding of 'inhibitors' and inhibit 'activators'. This leads to a closed chromatin structure in which genes are inactive. Thus, histone modification is, so to speak, signaling for the binding of regulatory factors.

2. Direct modification of the DNA histone structure

Some histone modifications, especially in the globular region at contact points between histones and DNA, can directly alter the chromatin structure. Some modifications promote the unwinding of the DNA from the histone nucleus (e.g., H3K122ac) and others promote the narrower coil (H3K64me).

Often, a combination of the above mechanisms is used to obtain the desired chromatin structure.

Summary

Histone proteins have globular areas that are wrapped in DNA.

Histone proteins have unstructured ends (N- and C-terminus) that protrude from the nucleosome structure.

Histones can be epigenetically modified in globular areas and at unstructured ends.

Histone modifications may promote or inhibit the binding of regulatory factors.

Histone modifications can directly alter the turn of DNA around histones.

These mechanisms alter the chromatin structure and thus the activity of genes in different parts of the genome.