DNA Packaging

One of the most complex and compact forms of packaging could be found in the way DNA is packed inside the cell. Although DNA is very tiny, at about 2.6 nm, it runs into lengthy ribbons that should be tightly wound into coils to be contained inside the cell.

A human cell contains 23 pairs of chromosomes. The diameter of a cell nucleus is only 2 micrometres inside which a 1.8 m long DNA has to fit in. Let’s look at the chromosome and travel deeper until we reach the DNA while understanding how it’s packed in every stage.

DNA Packaging

The length of a chromosome is 1400 nm with a 700 nm width. Chromosomes are tightly packed supercoils of chromatids which are 300 nm. These chromatids are further squeezed to form 250-nm wide fibres that run up and down like a wave.

A single chromatid is made up of multiple nucleosomes. A nucleosome combined with a protein named H1 histone is together called a chromatosome which are the building blocks of chromatids coils. A cluster of such nucleosomes combines to form a single coil of chromatid which is about 30 nm in diameter. A group of 6 such chromatosomes combine to form a structure called solenoids.

Eight proteins – H2A, H2B, H3 and H4 – a pair of each of these proteins clung together to form a single nucleosome. These 8 proteins are called core proteins. This set of 8 proteins is held in place using H1 histone and a DNA string is tightly wound around this structure looking like a bead in a string. The width of this structure (bead) is about 10nm. The stretch of DNA that runs between two beads linking them together is referred to as linker DNA. The H1 protein links with the linker DNA. The DNA string wraps around the nucleosome about 1.65 times.

These eight proteins (nucleosome) are high in lysine and arginine content making them slightly positively charged whereas the nucleotide of a DNA which has the phosphate, sugar and base group combination is negatively charged. These opposite charges help them bind together tightly.

During cell division, the components of the cell undergo a lot of changes and with it the DNA too. These core proteins help such changes to happen in the DNA during cell division. This process of changes happening in the DNA with the help of core proteins is collectively known as Covalent post-translational modification (PTM) which includes a variety of processes namely methylation, acetylation, SUMOylation, ubiquitylation and phosphorylation.

Epigenetics

Epigenetics is the phenomenon in which the PTM process lets the core proteins make changes in the DNA without making any changes to the nucleotide of the DNA. In other words, changes happen in the DNA without any gene mutation. These changes without affecting the nucleotides involve activating or deactivating transcription, chromosome packaging and repairing or damaging the DNA.

Hair-like fibres attached to the core proteins are called histone tails which aid in covalent post-transcriptional modification. Acetylation, phosphorylation and methylation are the major processes that occur using the histone tails while Ubiquitylation and SUMOlation happen at a comparatively reduced rate.

Transcriptional activation and inactivation

The chromatin can be accessed in two forms namely, euchromatin and heterochromatin.

• During the euchromatin stage, the DNA is expanded or loosely wound in between two nucleosomes making it easily accessible. This expansion helps to access the DNA and hence it is available for the transcriptional process.

• During the heterochromatin stage, the DNA is tightly wound with closely packed nucleosomes making it unable to access the DNA for the transcriptional process.

• Phosphorylation and acetylation aid the extension of DNA in the euchromatin stage. Methylation, ubiquitylation and SUMOlation together help both during the euchromatin and heterochromatin stages based on their availability around the DNA.

With the help of these two stages, the DNA can be activated or inactivated for the transcriptional process.

Acetylation & Deacetylation

During acetylation, the acetyl groups attach the histone tails of the tightly packed nucleosome – the heterochromatin stage. These acetyl groups, then, attack the lysome present in the core proteins to remove its positive charge. Once the core proteins lose their positive charge, it loosens their attachment with the DNA bringing it to the euchromatin stage. The acetyl group that aids the attachment with the histone group is called histone acetyltransferases. This complete process of bringing the chromatin from the heterochromatin stage to the euchromatin stage using the acetyl group is called acetylation.

The enzyme responsible for the removal of the acetyl group aiding in the deacetylation process is called histone deacetylases. During the deacetylation process, the acetyl group detaches itself from the histone tails giving back the positive charge to the core proteins which in turn helps them bind tightly with the DNA coil. This process is exactly the reverse of acetylation to make the nucleosome to its heterochromatin stage.

Methylation

Methylation helps both in converting the chromatin from euchromatin to the heterochromatin stage and vice versa depending on its location near the DNA. when a single methyl group (CH3) attaches to the core protein (or lysine) it is called monomethyl lysine. When two methyl groups attach to the protein it is called dimethyl lysine and when three methyl groups attach to the core protein it is then called trimethyl lysine.

The enzyme that helps in attaching the methyl group with the core proteins is called lysine methyltransferases while the enzyme that helps in the detachment of the methyl group from the protein is called lysine demethylase.

Phosphorylation

Just like methylation, phosphorylation aids in both euchromatin and heterochromatin stages. Phosphorylation acts on 4 proteins, namely − Tyrosine, Histidine, Serine and Threonine in which the phosphorus atom is attached to any one of these proteins. The enzyme that aids the attachment of the phosphorus atom to the protein is called Kinase. When a phosphorus atom is attached to the protein it knocks out the methyl group enabling demethylation and thereby activating the transcriptional process.

Depending upon the protein it acts on phosphorus atom carries out several functions. When attached to H4 protein it carries out mitosis, assembles chromatin and is also involved in inducing DNA damage. Apoptosis takes place when the phosphorus atom is attached to the H2AX protein.

Scientists are still researching this complex DNA model to come up with a better understanding of the processes that happen within the cell and to find a cure for diseases.

FAQS

Qns 1. What is DNA packaging?

Ans. The process in which very long ribbons of DNA are packed compactly into a tiny nucleus is collectively known as DNA packaging.

Qns 2. What are core proteins?

A pair of four proteins – H2A, H2B, H3 and H4 – these eight proteins are together called core proteins. These proteins combine to form the nucleosome.

Qns 3. What is meant by Covalent post-translational modification (PTM)?

Ans. During cell division, the components of the cell undergo a lot of changes and with it the DNA too. These core proteins help such changes to happen in the DNA during cell division. This process of changes happening in the DNA with the help of core proteins is collectively known as Covalent post-translational modification (PTM).

Qns 4. What is epigenetics?

Ans. Epigenetics is the phenomenon in which the PTM process lets the core proteins make changes in the DNA without making any changes to the nucleotide of the DNA.

Q5. What is meant by euchromatin and heterochromatin stages?

Ans. The chromatin can be accessed in two forms namely euchromatin and heterochromatin. During the euchromatin stage, the DNA is expanded or loosely wound in between two nucleosomes making it easily accessible. This expansion helps to access the DNA and hence it is available for the transcriptional process.