Chromatin structure is a unique attribute of eukaryotes and appears to be the key to the complexities associated with them. Because there is a vast amount of DNA present in eukaryotes, compaction into chromatin and subsequently a set of chromosomes is necessary. This is unlike prokaryotes because they have much less DNA that is typically stored in a single circular chromosome. Chromatin is a complex of DNA and proteins that are combined to form the chromosomes in eukaryotic nuclei. The main types of proteins that tend to associate with DNA are the histone proteins. The DNA wraps around an octamer of histone proteins creating what is known as the nucleosome. The histones that make up the octamer are called H2A, H2B, H3, and H4 histones [1]. The histone octamer is made up of two H2A/H2B dimers and one H3/H4 tetramer. The H2A/H2B dimers both form through a “handshake interaction” between their alpha helices. The H3 and H4 histones dimerize in this same way. Two of the dimers then come together and form a tetramer. This tetramer and two of the H2A/H2B dimers then bind to one another creating the histone octamer. The DNA is held to this histone core through a set of hydrogen bonds, which form along the amino acid chains of the histones and the backbone of DNA. Another type of bonding that hold the DNA to the histones are the salt bridges that form between positively charged lysine and arginine residues and the negatively charged DNA backbone [1]. Not all of the DNA can be wrapped around the histone core at all times; the DNA that is situated between the nucleosomes is known as linker DNA.
The nucleosome structures are considered to be on level one of DNA packing. This level of condensation of the DNA is not sufficient enough to fit all of the DNA into a cell. Therefore, an important structural aspect of the histone core is the N-terminal amino acid tails that are extended out from them. These tails allow for further compaction into what is known as the 30nm fiber. The histone tails allow for interaction between one nucleosome and another that is lying next to it [1]. Because of these interactions, any modification that occurs on the histone or histone tails can potentially alter the compaction of the chromatin structure. The tails are subject to covalent modifications such as acetylation (addition of the function group COCH3), methylation (addition of CH3), and phosphorylation (addition of a phosphate group). Acetylation occurs namely on lysine residues through the use of histone acetyl transferases (HATs). Lysine residues carry a positive charge on their nitrogen atom. Therefore, when a lysine is acetylated, the positive charge ceases on the nitrogen atom. This positive charge was allowing ionic interaction between the histone and the DNA backbone; therefore, the affinity of the acetylated tail to DNA has been reduced causing the chromatin to become less condensed. Another set of proteins, histone deacetylases (HDACs), causes the converse of this to happen by removing the acetyl group from the lysine residue [1]. The second type of modification mentioned was methylation, which occurs on both lysine and arginine residues by histone methyl transferases. Methylation can occur to varying degrees; lysine can be monomethylated, dimethylated, or trimethylated and arginine can also be mono- or dimethylated. Unlike acetylation, methylation does not remove the positive charge on the amino acid residue. Because of this, methylation does not particularly condense or decondense the chromatin, and each type of methylation can be recognized by a different protein or set of proteins. This can cause a variety of different effects on the chromatin structure [1]. A third type of covalent modification, phosphorylation, occurs on serine residues. This adds a negative charge to the histone proteins. Phosphorylation can have a variety of effects on chromatin structure. The modifications that occur on the tails can have a variety of meanings depending on the combination of said modifications. For example, the trimethylation on lysine 9 carries the meaning to create heterochromatin and thus gene silencing whereas the methylation of lysine 27 carries the meaning to silence HOX genes or to cause X-chromosome inactivation. These and other modifications on chromatin can be copied onto subsequent histones along a chromosome through the use of code-reader/code-writer complexes. The code-reader protein spots the modification code on a histone and binds to it. By doing this, the code-writer portion of the complex is in a position to make that same modification on the histone that is part of an adjacent nucleosome. Many of these complexes do not work alone; ATP-dependent chromatin remodeling complexes help them as well. These cycles of reading and writing code can either compact or loosen the chromatin [1]. There are also proteins that prevent the spreading of chromatin structure. These proteins are known as barrier proteins, and they interact with a sequence of DNA to position themselves in the way of reader-writer complexes. They may also reverse the modifications that were made through read-write cycles [1].
The four types of histone proteins that form the core of the nucleosome are important for many aspects of chromatin structure. Also important are variant histones. An example of one of these variants is CENP-A, a variant of histone H3. This variant histone is located only in centromeres, which are the center portions of chromosomes that are important for segregation of sister chromatids during the cell cycle. The chromatin in these regions is known as centric heterochromatin and is not decondensed even during the cell cycle [1]. The arrangement of the chromatin allows the centric heterochromatin to fold as to position these CENP-A variant-containing nucleosomes toward the outside of the chromosome. This allows for the formation of the kinetochore plates, which capture the microtubules from the mitotic spindle [1]. Other variant histones play important roles as well. For example, H2A variant H2AX functions in DNA repair and recombination and H2AZ in gene expression and chromosome segregation [1].
Edited by Ashley Lauren McPhee and Cheryl Ann Fleming