The manner in which DNA is stored in an organism's chromosomes is specific to each and every eukaryotic cell. For example, if the 48 million nucleotide pairs that are found in human chromosome 22 could be arranged into a single, perfect double helix, the molecule would have a length of approximately 1.5 centimeters when stretched from one end to the other. During mitosis, however, the length of chromosome 22 is only two meters, which indicates that the end-to-end ratio has been compressed by more than seven thousand times. This incredible feat of compression is due to the proteins that coil and fold the DNA into ever higher and higher levels of structure. These proteins are responsible for the compression. Even though they are not as densely packed as mitotic chromosomes, human interphase chromosomes still contain a high concentration of DNA.

It is essential to keep in mind that the form of the chromosome is shifting as you read through these sections. We have demonstrated that during the M phase of the cell cycle, each chromosome undergoes an exceptionally intense process of condensation. It is much less obvious, but of the utmost interest and significance, that specific interphase chromosome regions decondense in order to provide access to particular DNA sequences for gene expression, DNA repair, and replication, and then recondense once these processes are finished. Chromosomes are packaged in a manner that enables fast, on-demand localized access to the DNA. As a result, this access is made possible. In the following sections, we will discuss the particular proteins that are responsible for enabling this type of packaging.

Histones and non-histone chromosomal proteins are two groups of proteins that attach to the DNA to form eukaryotic chromosomes. Each of these protein types contributes nearly the same amount of mass to a chromosome as the DNA does. Chromatin is the collective noun for the two types of proteins that come together with the DNA in the nucleus of eukaryotic cells.

Histones are responsible for determining the initial and most fundamental level of chromosome packing, which is known as the nucleosome. This protein-DNA combination was discovered in 1974. When interphase nuclei are carefully sliced apart and their contents are examined with an electron microscope, the vast majority of the chromatin seems to be in the form of a fiber that has a diameter of approximately 30 nm. If the chromatin in question is subjected to procedures that cause it to partially unfold, then one can examine it under an electron microscope as a string of "beads." The string is also formed of DNA, but the beads are known as "nucleosome core particles." These particles are constructed of DNA that has been wound around a histone core.

The structural organization of nucleosomes was initially found after they were first extracted from unfolded chromatin by being digested with particular enzymes known as nucleases. These enzymes are responsible for breaking down DNA by slicing between the nucleosomes. Following a brief period of digestion, the linker DNA, which is located in an exposed position between the nucleosome core particles, is eradicated. The nucleosome core particle is formed by the combination of 147 nucleotide pairs of double-stranded DNA and eight different histone proteins. Specifically, the nucleosome core particle is composed of two molecules of each histone H2A, H2B, H3, and H4. A protein core is generated by the histone octamer, and the double-stranded DNA is wound around this core to create a twist.

The segment of linker DNA that separates one nucleosome core particle from the next can consist of as few as a few nucleotide pairs or as many as approximately 80 nucleotides. (A nucleosome, in scientific parlance, is composed of a nucleosome core particle and one of its adjacent DNA linkers; however, the phrases are usually used interchangeably.)

Because of this, nucleosomes normally repeat themselves once every 200 pairs of nucleotides. An example of this would be the fact that a diploid human cell has around 30 million nucleosomes and 6.4 109 nucleotide pairs. When nucleosomes are formed, a DNA molecule is converted into a chromatin thread that is approximately one-third of its initial length.

In 1997, researchers were able to identify the high-resolution structure of a nucleosome core particle. This structure showed that the nucleosome core contained a disc-shaped histone core that was securely enclosed in a left-handed DNA coil with 1.7 turns. The size of the four histones that are part of the nucleosome core can range from 102 to 135 amino acids, and they all have a similar structural pattern known as the histone fold. This pattern is composed of three helices that are connected by two loops. When the histone folds link to one another to produce a nucleosome, the H3-H4 and H2A-H2B dimers are generated. Additionally, when the H3-H4 dimers merge to form tetramers, the H3-H4 dimers become tetramers. The subsequent coupling of an H3-H4 tetramer with two H2A-H2B dimers produces the tight octamer core that the DNA coils around. This core is what gives the DNA its coiled shape.

The relationship between histone and DNA is a complicated one. There are 142 hydrogen bonds that connect the histone core to the DNA in each and every nucleosome. Together, the sugar-phosphate backbone of DNA and the amino acid backbone of histones are responsible for the formation of more than half of these connections. Salt bonds and other types of hydrophobic interactions are responsible for keeping the nucleosome in its proper place. More than one-fifth of each core histone is composed of lysine and arginine, which are two amino acids with basic side chains. Because of their positive charges, these amino acids are able to effectively balance the DNA backbone's negative charges. Because of these many interactions, DNA can bind to a histone octamer core even if it has a very different sequence than the histones themselves. Because the surface of the histone core is not perfectly smooth, the path that the DNA takes around it is not a straight one; rather, the DNA has a great number of kinks. In order for the DNA double helix to bend, the minor groove must be compressed to a sufficient degree. Some nucleotide sequences are able to attach to the nucleosome in a more secure manner than others, and certain dinucleotides in the minor groove are especially amenable to being compressed. This is most likely the explanation for certain astonishingly precise nucleosome arrangement along a stretch of DNA, even though such instances are rather rare. However, given that nucleosomes can be found in any one of a number of positions relative to the DNA sequence in the majority of chromosomal regions, their preference for one sequence over another must be weak enough to allow other factors to take precedence.

Each core histone consists of a histone fold as well as an N-terminal amino acid "tail" that extends away from the DNA-histone core. These histone tails are capable of undergoing a wide variety of covalent modifications, which, in turn, affect significant aspects of the structure and function of chromatin. We shall investigate these changes in a moment.

Histones play an essential role in DNA function through the regulation of chromatin structure, which is reflected in the fact that they are among the eukaryotic proteins with the highest degree of evolutionary conservation. Comparing the amino acid sequence of histone H4 from a cow and a pea, for example, reveals that there are just two spots where the two organisms differ. Because almost all of the amino acids found in histones have a role in the functions of the histones, it stands to reason that any shift in the position of these amino acids would be detrimental to the cell. However, in addition to this astonishing level of conservation, eukaryotic species also produce, albeit in much smaller quantities, variant core histones that are distinct from the primary ones in that they have a different amino acid sequence. These variations cause a variety of chromatin configurations in cells, which will be discussed later, along with the unexpectedly large number of covalent modifications that can be applied to the histones found in nucleosomes. These modifications can be applied to the histones found in the nucleosomes.