From Big Medical Encyclopedia

HROMATYN — the material substrate of chromosomes representing a multi-component system of the molecules which are in a certain space, chemical and physical relationship.

As the main structural and chemical component of chromatin serves the complex of deoxyribonucleic acid (see) with histones (see) and negistonovy proteins (see Nucleoproteids), sometimes — with protamins (see). Other components of chromatin — RNA (see P ibonukleinovy acids), lipids (see), carbohydrates (see), inorganic matters are directly or indirectly connected with proteins (see). Quantitative ratios of components of chromatin significantly depend on type of cells; their abundance most often corresponds to the following sizes: DNA of 30 — 45%, histones of 30 — 50%, negistonovy proteins 2 — 35%, RNA and other components 1 — 10%.

The term «chromatin» was entered in 1880 by the German scientist V. Flemming for designation of the painted structures of the fixed kernels of cells (except for kernels). The prevailing part of such structures is painted by the main dyes (bazokhromatin), and nek-ry — acid (oxychromatin). The chromatinic structures allocated in a kernel have an appearance glybok or networks of the fibrilla differing in one cell and in cells of different objects on a degree of dispersion. The most intensively painted blocks-ki — the chromocenters (karyosome) were called sometimes false kernels. It is lame the centers have, apparently, the increased adhesive ability as they easily contact with a nuclear envelope, and also aggregated with each other.

The structure of chromatin in kernels of interfazny cells, i.e. the cells which are in the period between the mitoses following one after another (see) depends on a stage of development of an organism (see Ontogenesis, Embryonic development). At a number of the studied objects in the first 2 — 4 blastomeres chromatinic structures do not come to light, at a stage of 8 — 10 blastomeres in a kernel the small chromatinic glybk getting in not sharing differentiated cells highly specific character for each type of cells come to light (see Cell division). In the course of aging of these cells observe strengthening of condensation of chromatin.

An isoelectric point (see) chromatin depends on amount of the proteins entering a complex with DNA and is in an interval of pH values 3,0 — 5,0. Patol. changes of chromatin as morfol. structures are followed by changes of pH, at to-rykh there is an isoelectric point. It is noted, e.g., at impacts of ionizing radiation, aging, etc. At various patol. states also the degree of dispersion of chromatin can change. So, tumor cells are characterized by existence of a large number of the chromocenters having sometimes rather large sizes; at a Down syndrome (see Down a disease) chromatin in comparison with norm is more condensed, constants of its linkng with dyes are changed; at Blum's syndrome (see the Poikiloderma) chromatin has the powdered or segmented structure. At nek-ry types of pathology strengthening of condensation of chromatin and concentration its large glybok on an inner surface of a nuclear envelope is noted (hyperchromatosis).

Structures of chromatin and a sex chromatin (see) observe by means of light microscopy. The form and the size of these structures depend on a way of fixing of cells. It demonstrates that the morphology of chromatin revealed after fixing reflects not its true structure in living cell, and only a possibility of different ways of its organization. In kernels of living cells, as a rule, the components corresponding to chromatinic structures do not come to light. However insignificant damages (irritations) in some cases lead to reversible emergence of such structures in before homogeneous kernel (e.g., at influence of narcotic analgetics, etc.). Also the opposite effect — the reversible «homogenization» of structures revealed normal in kernels of living cells is known. It is natural that optical homogeneity of a kernel is not identical to structural homogeneity of chromatin at the levels lower, than resolving power of light microscopy allows to see. Therefore now the term «chromatin» loses the morfol. contents, its thicket carry to chemical substrate of chromosomes (see) — to a difficult complex of biopolymers. Generally weak (not covalent) interactions organizing this complex in uniform system, as well as conformation (see) the molecules forming it, essentially depend on chemical structure, a quantitative ratio of the interacting components and external factors. It defines a possibility of various ways of the organization of a complex in general and (or) thanks to structural dynamics of the organization of its separate structural components. Believe that a set of such ways of the organization (states) is limited, and transitions between them have the nature of phase changes. Implementation of a condition of the chromatin for one reason or another not corresponding to a condition of this cell is normal, is a symptom of pathology.

Existence, at least, of two classes of chromatin is established: 1) euchromatin, to-ry it dekon-densirutsya during interphase and it is condensed in a mitosis; 2) heterochromatin, to-ry remains compact not only in a mitosis, but also in interphase where it is microscopically identified in the form of the chromocenters. Euchromatin is the main information part of a genome, in a cut structural genes with the respective regulatory areas are preferential localized. Late replication (see) DNA, being its part is characteristic of heterochromatin. Unlike euchromatin heterochromatin in the structural relation more labilen: sometimes observe its dekondensation at starvation, action of low temperatures, etc. It is established that at influence of a number of mutagen factors (see Mutagens) the chemical and physical nature structural damages are more often localized in heterochromatinic areas of chromosomes. Distinguish two types of heterochromatin. The first of them is the structural, constantly condensed chromatin. As a rule, it does not contain genes (see the Gene), its DNA is presented by generally short repeating nucleotide sequences (at nek-ry organisms — satellite DNA). At space rapprochement as a result of chromosomal reorganizations of sites of structural heterochromatin and euchromatin in some cases phenotypical manifestation of genes (a so-called position effect of a gene) is inhibited. Gene activation, localized in euchromatin, at space dissociation of the last with heterochromatin can be, according to some representations, one of the reasons of activation of the oncogenes localized in DNA of a chromosome. In general the role of structural heterochromatin is insufficiently clear. Believe that it sushchestven for processes of conjugation of chromosomes (see), a relative positioning of chromosomes in a kernel, attachments of sites of chromosomes to a nuclear envelope, laying of chromatinic fibrilla, protection of the vital elements of chromosomes, rapprochements of yadryshkoobrazuyushchy chromosomes, evolutions of a karyotype, etc. Thus, the estimated role of structural heterochromatin consists in regulation of the space organization and respectively — functional activity of chromosomes.

CHROMATIN 117 U of the person structural heterochromatin is localized in centromere sites of all chromosomes, in regions of secondary banners of chromosomes of the 1, 9, 16 couples, short shoulders of acrocentric chromosomes, in a distal part of a long shoulder of Y - chromosomes and frames blocks of genes of ribosomal RNA (yadryshkoobrazuyushchy areas). 10 — 15% of all chromatin fall to the share of structural heterochromatin at the person. At different persons the amount of structural heterochromatin varies even within homologous chromosomes. It is revealed that polymorphic options of structural heterochromatin (see Polymorphism in genetics) at people can correlate with nek-ry hereditary diseases, and it is possible to define them or to point out predisposition to them.

The second type of heterochromatin it is considered to be optional heterochromatin, or the inactivated euchromatin. This type of chromatin is similar to heterochromatin only in morfol. relation: microscopically it comes to light in an interfazny kernel in the form of intensively painted glybok the different size. Based on the molecular organization and functions, it is more correct to consider it one of types of euchromatin. It contains the structural genes phenotypical inactivated by condensation (geterokhromatini-zation) of euchromatin. One of typical examples of optional heterochromatin are little bodies Burra (X-chromatin).

Thus, functioning of chromatin as systems, in a cut happens the initial stage of implementation of hereditary information, substantially is defined by spacing its interdependent condensed and - the condensed zones (according to ideas of the physical processes which are the cornerstone of self-organization of spatial structure of chromatin — microphase stratification of system). Distribution of the condensed and dekondensiro-bathing zones is reflection of a condition of system in general that does not exclude, however, relative autonomy of these sites in a number of processes. Cases when by condensation of chromatin the inactivation of the whole chromosomes is carried out (e.g., are known to one of H - lame catfish at women) or almost all genome (e.g., in erythrocytes of birds). In the majority of types of cells the share of active chromatin makes 2 — 15%. According to a molecular biol. the analysis, in some cases the inactivation is connected with emergence of certain subfractions of a histone of H1 or substitution of the last other histones, in particular a histone of H5 (see Nucleoproteids). In spermatozoa of nek-ry animals repression of a genome is implemented against the background of substitution of histones by protamins or similar to them proteins.

The essential role to the organizations of a transcription (see), including through a differential dekondensation of chromatin, is taken to negistonovy proteins of chromatin (NGB). Their number includes also fermental complexes responsible for a reparation (see the Reparation of genetic damages), replication, a transcription and modification of nucleic acids (see) and for nek-ry enzymatic transformations of a number of chromosomal proteins. In kernels of cells, in to-rykh there is no active transcription, the amount of negistonovy proteins of chromatin is significantly reduced. E.g., mature gametes are substantially exempted from such proteins. Believe that the negistonovy proteins of chromatin which are strongly connected with DNA among take part in the organization or maintenance of a transcription to-rykh, apparently, there is a component which is specifically connecting a complex hormone — a receptor, and also the proteins of HMG14 and HMG17 which are closely connected with nucleosoma. The last are capable to inhibit deacetylation of histones, and this process along with I nedometilirovani-eat DNA represents the modifications characteristic of components of active sites of chromatin.

Ability of protein of A24 chromatin to splitting on histone N2a and polypeptide ubiquitin is important for structural transitions of chromatin. General characteristic of sites of transcriptionally active chromatin from different sources is hypersensitivity of their DNA to influence of a number of nucleases (see). At activation of a transcription such sensitivity extends to the site of molecule DNA as a part of chromatin on extent on about two orders more, than occupies a gene. Everything stated above testifies to value in the organization of a transcription of more high levels of packaging of chromatin, than its elementary fibrilla seen in a supermicroscope. H1, last with the participation of the histone, located along with negistonovy proteins of HMG1 and HMG2 chromatin generally on mezhnukleosomny DNA represents fiber diameter apprx. 10 nanometers. At the same time monotony of the nukleosomny organization of dezoksiribonukleoproteidny (DNP) fiber can be broken thanks to structural dynamics of nucleosoma (see the Cell), modifications of histones at their phosphorylation, acetylation, methylation and a ribozilirovaniye.

The essential part is assigned to the intermolecular contacts capable to regulate condensation of DNA at the level of nucleosoma. Nek-ry structural transitions of nucleosoma happen at change of ionic strength of the environment. In a kernel of a cell quantity of low-molecular antiions (ions of K+, Na +, etc.) in the order of size it is equal to number fixed on macromolecules (e.g., the DNA phosphatic groups) charges. Therefore small fluctuations in absolute quantity of low-molecular antiions in a kernel (e.g., at increase or reduction of volume of the last) shall cause structural transitions of nucleosoma. At last, the histone of H1 can be replaced with other histones or their complexes having bigger affinity to DNA with the corresponding reorganization of structure of fibrilla. Thus, the possibility of various ways of packaging of chromatin is put already at the level of various polymorphic structural options of elementary fibrilla of chromatin. Stability of the following level of the organization of chromatin — uneven on diameter (20 — 30 nanometers) of fibrilla — is provided, apparently, and a histone of H1. Further packaging of chromatinic fibrilla is implemented as believe, by self-organization of system with formation of the condensed (globular) zones and loops or independent superspi-ralizovanny areas (domains). Domains are characterized by the site of a double helix of DNA in a special way located in space, the ends of this double helix are fixed that limits or excludes a possibility of its rotation. Length of a loop of DNA on a contour for different objects corresponds a pier. to the weight (weight) of DNA about 10 000000 — 100 000000. Change of extent of super-spiralling of DNA is one more vazhnsh a factor of regulation of processes of an expression of genes (see Expressivity of a gene) through modification of supramolecular systems of chromatin. Superspiralling

of DNA changes also at action of ionizing radiation, some chemical compounds, activation of nucleases, etc. The specified factors cause single-stranded gaps in molecules DNA that leads to a relaxation in separate loops of its initial superspi-ralny structure. This process can cause redistribution of proteins of chromatin as a number of proteins has various constants of linkng with linear, ring and superspiral DNA.

Influence of the agents causing dissociation of proteins, in particular histones of chromatin (the nek-ry chemical mutagens ionizing the radiation, high salt contents, hydrogen ions, etc.), also leads to change of degree with at the Persian of a pi-ralnost as process of formation of nucleosoma is connected with reorganization of a superspiral of DNA.

Believe that the dynamic possibilities of structure of chromatin cannot be considered only as one of the factors regulating a transcription. Action of all other factors of regulation as inside - and extracellular, is implemented through creation of the structure of chromatin specific to each type of the cells differing on the nature of synthesis of RNA. In this regard all influences changing normal relationship between components of chromatin and by that — its structure shall bring to patol. to functioning of this system. The structural changes of chromatin contributing to the subsequent genetic trouble have essential value. So, believe that implementation of conditions of chromatin can be important, at to-rykh the probability of recognition by enzymes of a reparation of damages of DNA — the phenomena is reduced, a cut, apparently, serves one of the leading reasons of a phenomenon of instability of chromosomes and group of hereditary diseases, characteristic of them (see. Chromosomal diseases). Communication of nek-ry structural changes of chromatin with increase in frequency of conjugation of nonhomologous chromosomes — one of the possible reasons of aneuploidies is noted (see the Mutation). At action of genetically dangerous agents on cells and organisms except genetic damages of the DNA (genovariations) and the restructurings of chromatin stated above as systems arise numerous disturbances in interactions between components of chromatin: partial dissociation of proteins of chromatin, formation of intermolecular «stitchings» between DNA and proteins, disintegration of fibrilla of chromatin on nucleosoma, etc. that in turn strengthens patol. effect of such agent. Bibliography: Andreyev. And the Joint venture and t -

to about in with to and y D. M. Biophysical models of self-organization of spatial structure of chromatin, Dokl. Academy of Sciences of the USSR, t. 269, No. 6, page 1500, 1983; e about r and e in. Item and Bakayevv. B. Three levels of the structural organization of chromosomes eukaryote, Molek. biol., t. 12, No. 6, page 1205, 1978, bibliogr.; H e y f and x A. A. and T and m about f e e in and M. Ya. Problems of regulation in molecular biology of development, M., 1978; Prokofye - va - Bie lgovsky A. A. Znacheniye of negistonovy proteins in transformations and genetic functioning of chromosomes, Molek. biol., t. 16, Na 4, page 771, 1982; Theoretical problems of medical genetics, under the editorship of A. F. Zakharov, page 52, M., 1979; Chromatin structure and function, ed. by C. A. Nicolini, N. Y. — L., 1979.

D. M. Spitkovsky, H. A. Lyapunova.