Nucleosome: Structure, Function & Diseases

A nucleosome represents the smallest packaging unit of a chromosome. Together with linker protein and linker DNA, nucleosomes are part of chromatin, the material that makes up chromosomes. Autoimmune diseases of the rheumatic circle may develop in association with antibodies to nucleosomes.

What is a nucleosome?

Nucleosomes are composed of DNA wound around an octamer of histones. Histones are certain basic protein molecules that develop a strong binding force to the DNA chain. In particular, the abundant basic amino acids lysine and arginine provide the basicity of histones. The basic proteins can bind tightly to the acidic DNA to form the tightly packed structure of the nucleosomes. However, the nucleosome is only the most basic packaging unit of chromatin and thus of the chromosome. The discovery of nucleosomes was made in 1973 by Donald Olins and Ada via electron microscopic imaging of swollen cell nuclei. This revealed the so-called solenoid structure of DNA. This is the condensation of a larger number of nucleosomes into a chromatin fiber. This fiber looks like a coiled coil. The individual nucleosomes are linked together by the so-called linker histones, which are bound to the linker DNA, and form an organizational structure in chromatin known as a 30-nm fiber.

Anatomy and structure

The nucleosome consists of two basic components, histones and DNA. The histones first 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 histones of the same type each combine to form a dimer. The histone octamer in turn consists of the four different dimers. A DNA segment with 147 base pairs now wraps itself 1.65 times around the resulting protein complex and forms a left-handed superhelix structure. This winding of the DNA shortens its length by one-seventh from 68 nanometers to 10 nanometers. The digestion of the histones by the enzyme DNase results in the so-called nucleosome core particle, which consists of the histone octamer and a DNA fragment of 147 base pairs. The individual nucleosome core particles are linked together by the linker histone H1. The linker histone is simultaneously linked to the linker DNA. In turn, histone H1 represents a variety of protein molecules that vary depending on the tissue, organ, and species. However, they do not affect the structure of the nucleosome. When nucleosomes are joined by linker histone H1 and linker DNA, the so-called 30nm fiber is formed, which represents a higher level of organization of DNA. The 30nm fiber is a 30 nanometer thick chromatin fiber that is in the form of a coiled coil (solenoid structure). Histones are very conservative proteins that have hardly changed in the course of evolution. This is due to their fundamental importance in securing and packaging DNA in all eukaryotic organisms. Thus, the structure of nucleosomes is also the same in all eukaryotic cells.

Function and roles

The fundamental importance of nucleosomes lies in their ability to pack genetic material into the smallest possible space in the cell nucleus while keeping it safe. Even in less dense condensation states of chromosomes, very tight packing is still present. At the same time, however, enzymes in this case reach the DNA. Here they can then initiate a transfer of genetic information to mRNA as well as the synthesis of proteins. Nucleosomes also play a major role in epigenetic processes. Epigenetics is concerned with changes in the activity of genes in individual cells, which lead, among other things, to the differentiation of body cells into various organs. Furthermore, acquired characteristics are formed by epigenetic changes. However, the basic genetic structure of the hereditary material remains intact. However, various genes can be inactivated by tight binding to histones or by methylations, as well as reactivated by less dense packaging.

Diseases

There are diseases associated with nucleosomes. These are mainly autoimmune diseases in which the immune system produces antibodies against the body’s own proteins. Among others, nucleosomes can also be affected.Thus, in the systemic autoimmune disease lupus erythematosus (SLE), 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 probably plays a role in the pathogenesis. Elevated levels of circulating nucleosomes are found in the serum of patients. The free nucleosomes can induce inflammatory responses and induce cell death of lymphocytes. In addition, impaired degradation of nucleosomes, for example due to genetically reduced activity of deoxyribonuclease (DNase1), can lead to their increased concentration and thus to an increased risk of developing an autoimmune disease directed against nucleosomes, such as lupus erythematosus (SLE). Lupus erythematosus (SLE) is characterized by a very extensive clinical picture. Very different organs can be affected. Most commonly, symptoms appear on the skin, joints, blood vessels, and pleura. A typical butterfly-shaped erythema forms on the skin. This is intensified by exposure to sunlight. In addition to hair loss, there is also inflammation of the small blood vessels. When exposed to cold, Raynaud’s syndrome (white to bluish discoloration of the skin) is observed. Furthermore, extensive inflammation of the joints develops. When the kidneys are involved, the prognosis of the disease worsens due to the risk of renal failure.