Histones structure

The similarity of the various histone fibers is probably correlated with the similarity in the distribution of the amino acids in the sequences of the four core histones and reflects their function as the skeleton or backbone of chromatin. However, from the presence of a specific pattern of interactions of the core histones and the existence of histone variants and histone postsynthetic modifications, one can anticipate modulations in the basic general pattern of histone structure. In Section V, a possible mechanism for histone microheterogeneity influencing chromatin structure is suggested. Analogous to other assembly systems, small subunit modifications may be amplified to produce major changes in the assembled superstructure. 

Fig. 9. Accessory helices in core histone structures, (a) Accessory H3 helix, shown in a ribbon Ca model, interacts with the DNA entering and leave the nucleosome. A short helix in the tail of H2A is seen between the accessory and medial helix of H3. (b) Solvent accessible surface representation of the C-terminal residues of H2A showing the contribution of these residues to the ventral surface of the NCP.

M ethylation of Lys and Arg residues of histones has been identified as another tool for modification of histone structure and for regulation of transcriptional activity. The methylation of lysine residues of histones is an example of an epigenetic code that is used to establish transcriptionally inactive states both in heterochromatin and in euchromatin.The best characterized example is histone H3, which is found to be methylated at K4, K9 and K20. These methylations have a differential effect on transcriptional activity. 

The DNA lies on the surface of the histone octamer and makes about 1.75 left-hand superhelical turns about it. The structure of the octamer provides a helical "ramp" upon which the DNA is bound. Analysis of high-resolution data reveals a common histone structure called the "histone fold."... 

Since the histones themselves are phosphorylated, there may be competition with the DNA for binding to the positively charged regions of the histone proteins. The removal of OH in the phosphorylation process may also affect the H bonding system and thence the secondary and tertiary histone structure. 

Section 28 9 Within the cell nucleus double helical DNA adopts a supercoiled terti ary structure m which short sections are wound around proteins called histones This reduces the effective length of the DNA and maintains it m an ordered arrangement... 

If chromatin is swelled suddenly in water and prepared for viewing in the electron microscope, the nucleosomes are evident as beads on a string, dsDNA being the string (Figure 12.28). The structure of the histone octamer core has been determined by X-ray crystallography without DNA by E. N. Moudrianakis s laboratory (Figure 12.29) and wrapped with DNA by T. J. 

FIGURE 12.31 A model for chromosome structure, human chromosome 4. The 2-um DNA helix is wound twice around histone octamers to form 10-um uucleosomes, each of which contains 160 bp (80 per turn). These uucleosomes are then wound in solenoid fashion with six uucleosomes per turn to form a 30-nm filament. In this model, the 30-nm filament forms long DNA loops, each containing about 60,000 bp, which are attached at their base to the nuclear matrix. Eighteen of these loops are then wound radially around the circumference of a single turn to form a miniband unit of a chromosome. Approximately 10 of these minibands occur in each chromatid of human chromosome 4 at mitosis. 

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. 

Due to the large amount of DNA present within the nucleus it must be carefully packaged. In the resting cell DNA is tightly compacted around basic histone proteins, excluding the binding of the enzyme RNA polymerase II, which activates the formation of mRNA. This conformation of the chromatin structure... 

Repression of genes is associated with reversal of this process under the control of histone deacetylases (HDACs). Deacetylation of histones increases the winding of DNA round histone residues, resulting in a dense chromatin structure and reduced access of transcription factors to their binding sites, thereby leading to repressed transcription of inflammatory genes. 

Enzyme activity ascribed to corepressors, which is the removal of acetyl groups from lysine residues of histone tails. Thereby the assembly of nucleosomes is maintained, which leads to a dense, transcriptional inactive chromatin structure. 

Histone tails are the N-terminal regions of histones which reach outside the nucleosomes. They are not essential for the formation in of nucleosomes but are required for the formation of higher-order chromatin structures. The histone tails are also known to be heavily posttranslationally modified by acetylation, phosphorylation, methylation, etc. and are important for the regulation of gene activity. 

The nucleosome represents the first level of DNA condensation and is the basic building block of all chromatin structures. It was discovered in 1973 and consists of a central histone octamer with about 150 base pairs of DNA wrapped around. 

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