When the cell cycle is at the phase known as interphase, chromosomes present two types of chromatin under a light microscope: a highly condensed portion, known as heterochromatin, and a less condensed one, termed euchromatin. Euchromatin is the dispersed portion of chromatin that is transcriptionally active during interphase. In other words, euchromatin contains genes capable of transcribing genetic information into proteins that are necessary during interphase for young cells' maturation, metabolic functions, or DNA repair. Chromatin is comprised of DNA filaments and histone proteins, as well as some RNA molecules and constitutes the fibre of which chromosomes are made.
Euchromatin is found in two different states of condensation during interphase: about 10% is in the form of active euchromatin, thus being the less condensed form, while the remaining euchromatin remains in a more condensed state. However, the latter state is still less condensed than heterochromatin, which is also found in two degrees of condensation: at the chromosome's end and near the centromere heterochromatin is more condensed than in its remaining portions.
Heterochromatin and euchromatin are different in their biophysical conformations and in the metabolic expression of their genes, but not in their basic structures. For instance, in euchromatin the complex of histones, that constitutes nucleosomes, are more acetylated (i.e., bound to a greater amount of acetyl groups) than the interphasic inactive and more condensed portions of chromatin, known as heterochromatin. The presence of acetyl groups binding to histones in nucleosomes (acetylation) is crucial for the activation of the adjacent DNA into gene expression. Euchromatin is also richer in a minor variant form of the histone H2B, found in humans and in many other species. Euchromatic nucleosomes also bind to two members of a group of proteins called HMG or high-mobility-group proteins: HMGndash;14 and HMG-17. These proteins are found binding only to active chromatin and their amino acid sequences are highly conserved among different species. Another difference is that heterochromatin contains very low numbers of protein-coding genes and remains compacted in the first stages of interphase. At the ends of chromosomes' arms, heterochromatin is particularly highly condensed and this portion is also known as telomeres. Telomeres were first termed satellite DNA and believed to be not replicable. However, it was later discovered that telomeres are also replicated. Telomeres and the non-telomeric heterochromatin, i.e., the facultative heterochromatin, are replicated when these portions of DNA undergo a transition to euchromatin during cell proliferation, in different stages of the cell cycle. Telomeres are replicated through the mediation of the enzyme telomerase before DNA replication starts. Another group of enzymes, known as DNA polymerases, mediates both euchromatin and facultative heterochromatin replication.
In the last four decades, a large number of biochemical and biophysical researches have been performed aiming at the understanding and identification of the lipids, proteins and RNA molecules involved in the active control of euchromatin replication. Those and other current studies are crucial for the comprehension of the mechanisms involved in a number of genetic abnormalities and diseases, where the presence or the absence of a molecules involved in euchromatic control (known as epigenetic controls) may be implied in the silencing of one or more genes during DNA replication. Imprinting is an example of an epigenetic control that may lead to the silencing of specific genes during euchromatin replication. A silenced gene is not copied to the daughter cells and such an event, occurring either during conception or embryonic development, may lead to future serious illnesses, such as Prader-Willi syndrome, Angelman syndrome, and hydatidiform mole. Recent studies are also predicting the involvement of imprinting in Wilms' tumor, acute myelocitic leukaemia, lymphoma, and osteosarcoma. Some forms of imprinting can be potentially reversed through certain medications, now under intense scrutiny, such as the compound 5-aza-2'-deoxicitidine (AZA).
In summary, normal cell proliferation requires that all genes be copied before the division of a parent cell into two new daughter cells. When chromosomes are studied during early interphase, they present a discrete protein-coding activity that is not proliferative, i.e., directed to cell replication of DNA and further division. This activity is mainly due to cell metabolism, maturation (cell growth), or DNA repair. Euchromatin, the less condensed portions of chromatin, is responsible by this activity during the phases G0 and G1 of interphase. Before DNA duplication starts, the caps at the four ends of chromosome's arms, known as telomeres, are replicated. During DNA replication (phases S and G2), genes present in euchromatin are first duplicated because this portion is already in a less condensed state, and because this is the richer portion of chromatin in protein-coding genes. Afterwards, genes present in the facultative heterochromatin are also replicated, before cells undergo division into two new cells.
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