Chromatin: Structure, Function & Diseases

Chromatin is the material that makes up chromosomes. It represents a complex of DNA and surrounding proteins that can compress the genetic material. Disruptions in chromatin structure can lead to severe disease.

What is chromatin?

Chromatin is a mixture of DNA, histones, and other proteins bound to DNA. This forms a DNA-protein complex, but its main components are DNA and histones. The name chromatin results from the stainability of this complex with basic nuclear dyes. All eukaryotes contain chromatin. In prokaryotes, the DNA molecules are mainly free and form a ring structure. In higher eukaryotic organisms, chromatin is the basis of chromosomes. The DNA-protein complex can compress to such an extent that a great deal of genetic information can be stored in a small space in the cell nucleus. Histones are very ancient protein molecules whose genetic composition and structure have remained virtually unchanged from eukaryotic protozoa to humans.

Anatomy and structure

Chromatin, as mentioned earlier, is composed of DNA, histones, and other proteins. Within this complex, the DNA molecule is wrapped around a histone package of eight histones. Histones are proteins which consist of many basic amino acids. The amino groups generate a positive charge, while the DNA molecules have a negative charge on the outside. This is the basic requirement for the formation of a solid complex of DNA and histones. In this process, the so-called histone octamer (8 histones) is wrapped around approximately 1.65 times by the DNA double strand. This corresponds to a chain length of 146 base pairs. As a result, the DNA can be shrunk 10,000 to 50,000 times. This is necessary for it to fit into the cell nucleus. A unit of wrapped histone octamer is also called a nucleosome. The individual nucleosomes are in turn connected to each other by linker histones. Thus, a chain of nucleosomes is formed, which, as a 30nm fiber, represents a higher organizational unit of DNA. Even within the dense packing, the DNA can still be accessed by regulatory protein molecules that allow the genetic information to be read and transferred into proteins. However, a distinction must still be made between euchromatin and heterochromatin. In euchromatin, the DNA is active. This is where almost all active genes are located, which can code for and express proteins. There are no structural differences in the area of euchromatin, regardless of which condensation state the respective chromosome is in. Heterochromatin contains inactive or low-activity DNA-protein complexes. It is responsible for the structural nature of the overall chromatin. Heterochromatin, in turn, can be divided into two forms. Thus, there is constitutive and facultative heterochromatin. Constitutive heterochromatin is never expressed. It has structural functions only. Facultative heterochromatin can sometimes be expressed. During the different phases of mitosis and meiosis, different packing levels of chromatin are formed. In this process, the so-called interphase chromatin shows a very strong loosening compared to metaphase chromatin, since most proteins are expressed in this state.

Function and tasks

The function of chromatin is to accommodate genetic information in the very small space of the nucleus. This is only possible through the formation of a very tightly packed DNA-protein complex. However, this requires the existence of different condensation stages. While the complex is very densely packed in a quiescent and inactive phase, it must be more loosened up in more active phases. But even here, the packing is still very dense. To activate protein synthesis, the strong binding between the corresponding DNA segments and the wrapped histone must be released. The bound histones block the DNA from expressing proteins. Thus, different binding states can also produce different activities of the genes. In this process, cell differentiation occurs as part of epigenetic processes. Although the genetic information of DNA is the same in different body cells, the activities in gene expression are different, so that different cell types also perform different tasks.

Diseases

Defects in the structure of chromatin can lead to serious diseases.These errors can result in activity shifts in gene activity, which disrupt the harmony in the interaction of the body’s cells. These are often very rare diseases whose symptoms are very similar. The affected individuals suffer from physical deformities and mental disabilities. The mechanisms that cause these symptoms are still too little known. However, research into these relationships is necessary in order to be able to treat these diseases in the best possible way. Two typical diseases based on chromatin disorders are Coffin-Siris syndrome and Nicolaides-Baraitser syndrome. Both diseases are genetically determined. In Coffin-Siris syndrome, congenital hypoplasia of the finger and toe bones, short stature and mental retardation occur. There are various mutations responsible for triggering this disease, which are responsible for certain subunits of the DNA-protein complex. There are both autosomal recessive and autosomal dominant inheritances. Treatment is symptomatic and depends on the particular pronounced symptoms of the disease. Nicolaides-Baraitser syndrome also presents with similar symptoms. In addition to short stature and malformation of the fingers, severe mental retardation and seizures also occur. Inheritance is autosomal dominant. The disease is very rare and occurs in one in a million people. Another rare hereditary disorder associated with a chromatin disorder is Cornelia de Lange syndrome. This syndrome also has many physical malformations and intellectual developmental disorders.