Nucleosome

A Nucleosome represents the smallest packaging unit of a chromosome. Together with the linker protein and the linker DNA, the nucleosomes belong to the chromatin, the material from which the chromosomes are made. In connection with antibodies against nucleosomes, autoimmune diseases of the rheumatic circle can develop.

What is a nucleosome?

Nucleosomes are made of DNA wrapped around an octamer of histones. Histones are certain basic protein molecules that develop a strong bond with the DNA chain. The frequently occurring basic amino acids lysine and arginine in particular ensure the basicity of the histones.

The basic proteins can bind firmly to the acidic DNA and thus form the tightly packed structure of the nucleosomes. However, the nucleosome is only the most elementary packaging unit of the chromatin and thus the chromosome. The discovery of the nucleosomes took place in 1973 by Donald Olins and Ada through the electron microscopic representation of swollen cell nuclei. The so-called solenoid structure of DNA was revealed. It is the compression of a large number of nucleosomes into a chromatin fiber.

This fiber looks like a coiled coil. The individual nucleosomes are linked to one another by the so-called linker histones, which are bound to the linker DNA, and form an organizational structure in the chromatin known as a 30 nm fiber.

Anatomy & structure

The nucleosome consists of two basic components, the histones and the DNA. The histones initially form a histone octamer. This represents a protein complex of eight histones. The basic building blocks of this complex are four different histones. These include the proteins H3, H4, H2A and H2B. Two identical histones each combine to form a dimer.

The histone octamer in turn consists of the four different dimers. A section of DNA with 147 base pairs now wraps 1.65 times around the resulting protein complex and forms a left-handed superhelix structure. This twisting of the DNA reduces its length by a seventh from 68 nanometers to 10 nanometers. During the digestion process of the histones by the enzyme DNase, the so-called nucleosome core particle is created, which consists of the histone octamer and a DNA fragment of 147 base pairs.

The individual nucleosome core particles are connected to one another by the linker histone H1. The linker histone is also linked to the linker DNA. The histone H1 in turn represents a multitude of protein molecules that vary depending on the tissue, organ and type. However, they do not affect the structure of the nucleosome. When the nucleosomes are connected by means of linker histone H1 and linker DNA, the so-called 30nm fiber is formed, which represents a higher level of DNA organization.

The 30nm fiber is a 30 nanometer thick chromatin fiber in the form of a wound coil (solenoid structure). The histones are very conservative proteins that have hardly changed in the course of evolution. This is due to their fundamental importance for securing and packaging the DNA in all eukaryotic living beings. The structure of the nucleosomes in all eukaryotic cells is the same.

Function & tasks

The fundamental importance of nucleosomes lies in their ability to package the genetic material in the smallest space in the cell nucleus and at the same time to secure it. Even with less dense condensation states of the chromosomes, the packaging is still very tight. At the same time, however, enzymes reach the DNA in this case.

Here they can then initiate the transfer of the genetic information to the mRNA and the synthesis of proteins. The nucleosomes are also of great importance in epigenetic processes. Epigenetics is about changes in the activity of genes in individual cells, which, among other things, lead to the differentiation of body cells into different organs. Furthermore, acquired characteristics develop through epigenetic changes.

However, the basic genetic structure of the genetic material is retained. However, various genes can be inactivated by binding to histones or by methylation, and they can be reactivated by less tight packaging.

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Diseases

There are diseases that are related to nucleosomes. These are mainly autoimmune diseases in which the immune system forms antibodies against the body's own proteins. Among other things, nucleosomes can also be affected.

In the systemic autoimmune disease lupus erythematosus (SLE), the nucleosomes represent antigens that are attacked by the body's own immune system. In the development of systemic lupus erythematosus (SLE), the combination of genetic factors with environmental influences plays a role in the pathogenesis. Increased concentrations of circulating nucleosomes are found in the serum of the patients. The free nucleosomes can induce inflammatory reactions and cause the cell death of lymphocytes. In addition, an impaired breakdown of nucleosomes, for example due to a genetically determined reduced activity of the deoxyribonuclease (DNase1), can lead to its increased concentration and thus to an increased risk of developing an autoimmune disease such as lupus erythematosus (SLE) directed against nucleosomes.

Lupus erythematosus (SLE) is characterized by a very extensive clinical picture. Very different organs can be affected. Symptoms most often appear on the skin, joints, blood vessels and pleura. A typical butterfly-shaped erythema forms on the skin. This is intensified by solar radiation. In addition to hair loss, the small blood vessels also become inflamed. Raynaud's syndrome (white to bluish discoloration of the skin) is observed when exposed to the cold. Extensive joint inflammation also develops. If the kidneys are involved, the prognosis of the disease worsens due to the risk of kidney failure.