Histones composition

Of important note, native nucleosomes are intrinsically heterogeneous both in terms of their DNA sequence and histone compositions and both of which can contribute to the stability of the complex. 

Although the histones prepared from various cell types in the chick are very similar, the histones from rooster testes and chicken erythrocytes differ considerably from the histones obtained from other tissues. Minor but consistent differences have been observed in the histone composition at various stages during the development of the chick embryo the significance of these findings remains to be established. The differences between histones of tumor cells and histones of normal tissues are discussed in greater detail in the chapter devoted to cancer. 

Chromatin is composed of nucleosomes, where each comprise 147 base pairs of DNA wrapped around an octamer oftwo copies of each histone H2A, H2B, H3, and H4. Nucleosomes are folded into higher-order structures that are stabilized by linker histones. Chromatin structure can be altered by enzymes that posttranslationally modify histones (e.g., through phosphorylation, acetylation, methylation, or ubiquitination) or by ATP-driven chromatin-remodeling complexes that alter nucleosome position and/or composition. 

In this connection, it must also be borne in mind that the deoxyribonucleic acids subjected to analysis have probably not been homogeneous. Deoxyribonucleic acids have been fractionated by making use of their different solubilities in normal saline,186 by extracting thymus nucleo-his-tone with sodium chloride solutions of increasing concentration,187 by ion-exchange,187 and also by adsorption of the polynucleotide onto histone immobilized on a kieselguhr support.123 It is possible, however, that these are artefacts, since it has been shown that deoxyribonucleic acid fractions extracted from calf-thymus nucleohistone may or may not vary in composition according to the previous treatment of the material.188... 

Fig. 17. Composite structural motions of subunits can be described with translation, libration, and screw-axis (TLS) analysis of the NCP. Analysis of the histone subunits are shown here, (a) Composite motion of histones H2A (blue) and H2B (blue) considered as individual elements and combined as H2A H2B dimer (red). Note for the individual histones that the axis of motion is parallel with the medial a-helix of the histone. The origin of the TLS axes are within the structural positions of the histone. The composite motion for the H2A H2B dimer is dominated by the motion of H2A, as is seen in the similarity of orientation and position of the two axes, (b) The orientation and motion of the two H2A H2B dimers appear symmetric across the dyad axis of the NCP. (c) H3 H4 composite motions when considered as dimers (blue) and as the tetramer (red). Interpretation is more complex because of the asymmetric magnitude of motion for the two dimers, and the different position in the axis of primary motion for the tetramer. These motions are most likely the consequence of packing interactions, described in greater detail in the text.

Fig. 19. TLS analysis of the NCP, DNA, and histone core. In these ventral and dorsal views of the NCP model, the composite motion axes of the DNA, histones, and the NCP are shown in red, blue, and green, respectively. The center of motion axes for the DNA and the histones are non-coincident, the TLS axis for the DNA is furthest from the center of mass of the NCP. This may reflect the dominance of the DNA ends in the overall displacement of the DNA. The TLS analysis shows that DNA regions with high B-values, seen in Fig. 15, have little contribution to the overall motion of the DNA on the NCP. The overall motion of the NCP appears dominated by the DNA motion, with the TLS origin shifted in the direction and appearing congruent with the DNA. Overall, the primary axes of motion are in plane with the DNA, hence the interpretation that the composite motions are dominated by dynamic tension between the DNA and the histones, with deviation from these general motions the consequence of packing interactions.

The above general scheme based on comparisons of the most evolutionarily conserved GHl domain does not reveal the rich microheterogeneity of linker histones which stems from differences between the less well conserved basic tails. Such variants, often referred to as somatic subtypes, occur in plants (for review see Ref. [80]) and animals, both invertebrates and vertebrates (for review see Refs. [81-83]). For example in mammals five somatic subtypes represent the major form of HI HF-1, HF-2, HF-3, HF-4, and HI a, according to the nomenclature proposed in Ref. [82]. The N- and C-terminal tails of the subtypes differ in length, the amino acid composition and the frequency and distribution of phosphorylation sites. The testis specific Hit can be considered the most diverged subtype of the major form. 

In recent years it has become increasingly apparent that the compositional heterogeneity of the chromatin fiber through histone variants, histone post-translational modifications and chemical modifications of DNA (methylation) [9] play an important role in all these processes. The different sources of compositional heterogeneity are described in Sections 2-4 of this review. 

Duerre, J.A. and Chakrabarty, S. (1975) Methylated basic amino acid composition of histones from the various organs from the rat. J. Biol. Chem. 250, 8457-8461. 

Histone acetyltransferases (HATs) are enzymes that acetylate specific lysine residues in histones through the transfer of an acetyl group from an acetyl-coenzymeA (AcCoA) molecule, causing profound effects on chromatin structure and assembly as well as gene transcription. HATs are found in most, if not all, eukaryotic organisms as multiprotein complexes, some HAT catalytic subunits even being shared between various complexes that display different substrate specificities based on their subunit composition [12]. Despite their name, HATs do not restrict themselves to the acetylation of histones, since these enzymes have also been shown to act on nonhistone proteins, broadening their scope of action [13]. 

Except the protamines, the histones and the derivatives of the proteins, all the proteins contain carbon, hydrogen, nitrogen, sulphur and oxygen, and they possess the following elementary composition —... 

Found in the chromatin of all eukaryotic cells, histones have molecular weights between 11,000 and 21,000 and are very rich in the basic amino acids arginine and lysine (together these make up about one-fourth of the amino acid residues). All eukaryotic cells have five major classes of histones, differing in molecular weight and amino acid composition (Table 24-3). The H3 histones are nearly identical in amino acid sequence in all eukaryotes, as are the H4 histones, suggesting strict conservation of their functions. For example, only 2 of 102 amino acid residues differ between the H4 histone molecules of peas and cows, and only 8 differ between the H4 histones of humans and yeast. Histones HI, H2A, and H2B show less sequence similarity among eukaryotic species. 

What feature of the amino acid composition of histones enables them to interact strongly with DNA ... 

Clarke, H.J., Oblin, C., and Bustin, M. (1992). Developmental regulation of chromatin composition during mouse embryogenesis Somatic histone HI is first detectable at the four-cell stage. Development 775 791-799. 

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