In cells, systems of this nature are responsible for a great many important activities. The fact that certain chromatin structure types can be passed down directly from one cell to its offspring is the most remarkable feature. This is an example of epigenetic inheritance because the resulting cell memory is based on an inherited chromatin structure rather than a change in the DNA sequence. This is in contrast to genetic inheritance, which would involve a change in the DNA sequence. Given that epigenetics refers to a form of inheritance that is added to genetic inheritance based on DNA, the prefix epi, which means "on," comes from the Greek word for "on." This is fitting, given that epigenetics is a term.

In this particular instance, the only one that piques our curiosity is the one that is based on the structure of the chromatin. This section will begin by discussing the observations that initially demonstrated that chromatin configurations can be passed down from one generation to the next within families. Following this, we will discuss some of the chemistry that is involved in the covalent modification of histones within nucleosomes, which is what enables this process to take place. These modifications serve a variety of functions because they are responsible for connecting specific protein complexes to different regions of chromatin and therefore act as protein domain recognition sites. Therefore, histones have an effect on a variety of processes that are related to DNA, including the expression of genes. These mechanisms are responsible for the development, growth, and maintenance of all eukaryotic organisms, including humans; this fact highlights the significance of chromatin structure in the aforementioned processes.

Light microscopy experiments performed in the 1930s differentiated two forms of chromatin found in the interphase nuclei of many higher eukaryotic cells: a highly condensed portion of chromatin referred to as heterochromatin and the remainder of chromatin, which is less condensed and referred to as euchromatin. We are just now beginning to have a grasp on the molecular properties of heterochromatin, which is a kind of chromatin that is unusually dense. It is most concentrated at the centromeres and telomeres, which have already been described, but it is also present at a great number of other places along the chromosomes. These other places along the chromosomes can alter depending on the physiological state of the cell. In a typical mammalian cell, this type of packaging accounts for more than ten percent of the genome.

Since heterochromatin typically contains just a small number of genes, the majority of euchromatic regions' gene expression is normally silenced during the process that converts those regions to a heterochromatic state. However, as of this day and age, we are aware that the term "heterochromatin" refers to a number of different forms of chromatin compaction that affect gene expression in a variety of different ways. Therefore, heterochromatin should not be considered as exclusively containing "dead" DNA; rather, it should be understood as a word for compact chromatin patches that have the shared trait of being very resistant to gene expression.

During the process of chromosome breakage and rejoining, a fragment of a chromosome that is ordinarily euchromatic can be moved into the region of heterochromatin. This can happen whether the breakage is triggered by a spontaneous genetic accident or by the experimental artifice of a scientist. Surprisingly, this frequently leads to the silencing or inactivation of genes that are normally very active in the body. This phenomenon is referred known as the location effect in linguistic parlance. This phenomena, which portrays the extension of the heterochromatic state into the initially euchromatic zone, has been a huge help to the mechanisms that make and maintain heterochromatin. It has been an enormous source of support for these mechanisms. Although position effects were first seen in Drosophila, they have now been found in a wide variety of eukaryotic organisms, such as yeasts, plants, and even humans.

During chromosome breakage and rejoining events of the sort that were just described, the zone of silence, which is where euchromatin is transformed to a state of heterochromatin, extends for varied distances in different early cells in the fly embryo. During these types of events, the fly embryo. Surprisingly, once the heterochromatic condition has been created on a portion of chromatin, it has a tendency to be consistently inherited by all of the children of that cell. This helps to maintain these distinctions for the remainder of the animal's life. This extraordinary phenomenon, which is referred to as position effect variegation, was originally noticed in the eye of the fly when it appeared as a patchy loss of red pigment. It is comparable to the ubiquitous presence of heterochromatin, which, in female animals, causes one of the two X chromosomes to become inactive. A similar random process determines which X chromosome will be inactivated in each early embryonic cell, and that same X chromosome then remains inactive in all of the cell's progeny, resulting in a mosaic of different clones of cells in the adult body. This causes the body to have a variety of different types of cells.

These discoveries are all connected to the fundamental concept behind the creation of heterochromatin, which is that heterochromatin reproduces itself. This positive feedback can work both spatially (causing the heterochromatic state to propagate along the chromosome) and temporally (causing the heterochromatic state to propagate along the chromosome), allowing the heterochromatic state of the parent cell to be passed on to its daughters. Finding the chemical pathways that are responsible for this unusual behavior is the challenging portion of the investigation.

The first thing one can do is conduct a search for the chemicals that are of interest. This has been accomplished through the utilization of genetic screens, in which a large number of mutants are created and then picked based on whether or not they display an abnormality of the process that is of interest. Through thorough genetic screening in Drosophila, fungus, and mice, researchers have identified more than one hundred genes that either enhance or decrease position effect variegation. These genes are accountable for the propagation of heterochromatin as well as its inheritance in a consistent manner. It has come to light that many of these genes are responsible for the production of non-histone chromosomal proteins. These proteins interact with histones, which in turn change or maintain the structure of chromatin. In the sections that are to come, we are going to discuss how they operate.

Some of the covalent modifications that are applied to the amino acid side chains of the four histones that make up the nucleosome core include the phosphorylation of serines, the acetylation of lysines, and the mono-, di-, and trimethylation of lysines. Other covalent modifications include the trimethylation of lysines. A considerable majority of these side-chain alterations occur in the eight very unstructured N-terminal "histone tails" that protrude from the nucleosome (Figure 4–34). In addition, there are about 20 different side-chain modifications that can be found on the globular core of the nucleosome.

All of the alterations that have been described up until this point are capable of being undone; although one enzyme is required to bring about a particular kind of change, a different enzyme is necessary to undo it. These enzymes fall into a very specific category. Therefore, for example, a number of different histone acetyl transferases (HATs) add acetyl groups to particular lysines, while a number of different histone deacetylase complexes remove those acetyl groups (HDACs). In a manner comparable to this, various histone methyl transferases add methyl groups to lysine side chains, while numerous histone demethylases remove these methyl groups. Each enzyme, at a given time in the life cycle of the cell, is drawn to a specific spot on the chromatin. These times and places are predefined. The first recruitment is driven mostly by transcriptional regulator proteins, sometimes known as "transcription factors." These proteins are substantially responsible for the process.