Around 3 billion base pairs of nucleotides are available in the human genome. There is a linear sequential arrangement of these nucleotides along DNA. This encodes every protein and genetic trait in the human body. DNA sequencing or genetic sequencing is important for normal cell function and is highlighted when the anomalies go undetected by intrinsic genetic repair mechanisms and thus resulting in dysfunctional proteins and various disease states.
The DNA sequence is maintained through a series of processes and is condensed into 46 chromosomes in Humans. The number of chromosomes varies for every species. These chromosomes undergo further condensation through two ways called mitosis or meiosis. On the other hand, interphase chromosomes also undergo a series of events like DNA folding, wrapping, and bending which are facilitated by Histones. The combination of DNA and Histone proteins in the nuclear matter is termed as Chromatin.
Chromatin consists of 1147 base pairs of DNA wrapped around the protein core histone. The histone is made of 2 units of H2A, H2B, H3, and H4 forming an octamer.
The chromatin in the interphase is generally classified into two parts:
A region in which DNA is accessible and is present in an open confrontation because of the relaxed state of nucleosome arrangements is referred to as Euchromatin.
Euchromatin majorly has unmethylated first gene exons. They exist in decondensed form and are present in the distal arms of the chromosome. Euchromatin is spread all around the nucleus and is replicated during the whole S Phase. It is generally known as the transcriptionally active form of chromatin. Euchromatin has less compact structure and is usually referred to as 11 nm fiber with the presence of beads on a string. The beads represent nucleosomes and string refers to DNA.
The chromatin which is involved in the active transcription of DNA into mRNA is euchromatin. As euchromatin is more open in order to allow the recruitment of RNA polymerase complexes and gene regulatory proteins, so transcription can be initiated.
A functionally different genomic compartment which has relatively low gene density along with a highly compact chromatin structure is referred to as heterochromatin.
There are two kinds of Heterochromatin: ‘Constitutive Heterochromatin’ is virtually present in all stages of an organism's life cycle. ‘Facultative Heterochromatin’ occurs in one of a pair of homologs. Heterochromatin can epigenetically administer the expression of nearby genes resulting in varied phenotypes in genetically identical cells.
Biochemical and genetic approaches show that the RNAi machinery plays an important role in the formation of heterochromatin.
The structure of Heterochromatin is tightly packed and condensed. The changes in heterochromatin occurs due to the modifications to histones and spreading of silencing complexes cause the changes in structure of chromatin. Due to its repressive structure, heterochromatin does not completely express the genes within it.
Heterochromatin usually folds into higher order structures and this induces an increase in negative supercoiling of DNA. The structure of Heterochromatin is stable and is also dynamic that changes with cell cycle. The formation of chromatin is promoted due to the DNA elements called barriers which promote the formation of active chromatin and remove the nucleosomes. This allows the heterochromatin to spread.
The structure of Heterochromatin is easily explained by analysing the ‘Constitutive Heterochromatin’ and ‘Facultative Heterochromatin’. Constitutive Heterochromatin is the stable form which consists of repeated sequences of DNA called Satellite DNA. The structural functions are regulated by this form of heterochromatin and are found in centromeres and telomeres.
Facultative Heterochromatin is known to change its structure according to the cell cycle. This consists of repeated DNA sequences termed as ‘LINE Sequences’. This can be seen to change its structure in the inactivated X-chromosome of females. The structure of heterochromatin can also be determined by the density gradient data in which the heterochromatin appears as regular structure and euchromatin has an irregular structure.
The functional aspects of heterochromatin are determined by the modifications of chromatin. The heterochromatin core histones present in yeast are hypoacetylated which makes the lysine residues to become more positively charged, allowing an increase in the interaction between the histone and DNA, making the nucleosome more closed in structure.
The closed chromatin structure of heterochromatin is due to the low acetylation of Histone H4-K16 in heterochromatin, further promoting the folding of chromatin to high structure orders. The active transcriptional activity is due to the hypomethylation of heterochromatin at H3-K4 and K79.
1. Why is Euchromatin Transcriptionally Active?
Euchromatin is available in transcriptionally active cells because of its accessibility to DNA, folding into heterochromatin to regulate the transcription by preventing the access of RNA polymerases and other regulatory proteins to the DNA.
2. What is Heterochromatin Used for?
There are several functions for heterochromatin, starting from the gene regulation to the protection of chromosome integrity. These roles can be related to the dense packing of DNA which allows limited accessibility to protein factors which usually bind DNA or its associated factors.