What are histones?
- They are a group of highly alkaline relatively small proteins, and they have a strong positive charge because they have a high content of amino acids, for example, Lysine and Arginine, and are present in the eukaryotic cell nuclei. These are the basic amino acids and they give the histones a positive charge. The DNA is negatively charged and the binding of DNA with the histones is stabilized by the ionic bonding. These opposite charges help the binding of the DNA with histone proteins, known as Nucleosomes.
- Histones were discovered in 1884 by Albrecht Kossel. It is very important to maintain the pH of the histone because at below pH 4, they lose their specific secondary and tertiary structure, undergo non-specific aggregation, and become partially unfolded.
- Histones play an important role in maintaining the structure of chromosomes. Within a nucleus, DNA is present and its length is about one meter or more if we extend it completely while the diameter of the nucleus is not more than 5-10nm. The folding of this wide length of DNA into a nucleus that is a million times smaller than the DNA is a very odd thing.
- Chromosomal DNA is hierarchically coiled. The structure of chromosomes is highly ordered in the eukaryotic cell and each chromosome undergoes a certain level of condensation or complexity. DNA is complex with several proteins and to achieve this level of complexity DNA undergoes coiling and sub coiling to form the chromatin. DNA is a 2nm thick double helix. To fit into the cell nucleus and for the purpose of giving the chromosomes a more compact shape, DNA wraps itself around the complexes of histone proteins.
Types of histones
There are five main types of histones
These types are divided into two main classes.
- The core histones are H2A, H2B, H3, and H4.
- The linker histones are H1 and H5 (highest Lysine and Arginine ratio). The linker histones are involved in the highly ordered structure of chromatin. For the formation of a highly ordered structure of DNA, the linker histone protein H1 locks the DNA into place by binding with the nucleosomes at the starting and ending sites of DNA. H5 histones are individual proteins and play an important role in the packaging of a specific region of DNA. The mass of the histones in chromatin is approximately equal to the mass of the DNA in most cells.
An equal volume of H2A, H2B, H3, and H4 molecules are present in chromatin but about half of that number of H1 molecules. In different kinds of eukaryotic cells, this proportion remains constant.
Functions of histone
- The basic function performed by them is that they bind with the DNA and help the DNA to maintain its shape and control the activity of genes.
- An active gene is less bound by histone as compared to an inactive gene that is highly bound by histone. Particularly all the types of nuclei contain histone proteins. They have basic properties and play an important role in the regulation and function of chromosomal DNA.
- These proteins also play an important role in regulating replication and DNA transcription, in simple words, they regulate cellular events.
Structure of Histones
- The structural pattern of the Core histones is known as the Histone fold domain (The 3D structure of a protein is determined by the amino acids sequence and the folding of proteins in their correct local structure is very important to perform their function). They are formed by three alpha helices which are connected with each other by two loops.
- Histones are made up of high content of basic amino acids, Lysine and Arginine that give them a positive charge, and this negative charge help in binding with the negatively charged DNA.
- Histone octamer – It is formed by the complex of eight proteins that are present at the center of the Nucleosome core particle and these proteins play an important role in the packaging of DNA. Histone Octamer is made up of two copies of each of the histone proteins H2A, H2B, H3, and H4.
- The nucleosome is made up of eight histones molecules or proteins (two H2A-H2B dimers and H3-H4 tetramers) forming a tertiary structure and these histones proteins are wrapped by a stretch of 147 base pairs of double stranded DNA. The DNA and proteins bind together by Salt linkages (unstable ionic nature bonding). They are called Salt linkages because of specific metallic ions for example Ca++ and Mg++. Nucleosomes bind with the other Nucleosomes with the help of the linker DNA having a short length of 8 to 147 base pairs. The diameter of the nucleosome is 10nm. In the nucleosome, histone proteins have tails known as N-terminal tails. These tails are made up of specific amino acids and undergo various translational modifications preferably Acetylation, Phosphorylation, and Methylation with the help of these terminal tails. With the help of these tails different proteins can bind to chromatin and as a result, affects the chromatin condensation and transcriptional activity. Nucleosomes are then packed together to form chromatin fibers and chromosomes.
- Solenoid – When the chain of the nucleosomes (consisting of Six nucleosomes) is wrapped into a 30nm spiral it will call a Solenoid. In simple words, we can say that it is a condensed chromatin fiber with a diameter of 30nm and play its role in DNA packaging. Chromatin fibers look like beads on a string, the beads represent the proteins and the string represents the DNA when the DNA is wrapped around the protein it will be known as a nucleosome. The chromatin fibers present in the chromatin have a diameter of 10nm but in intact cells, chromatin forms a thick fiber 30nm in diameter called solenoid.
Effect of Histone modification on chromatin packaging
- Eight Histones proteins have tails known as N-terminal tails which can undergo chemical modifications. These modifications can take place either by the addition or removal of the acetyl and methyl groups. Nucleosomes loose packaging is favored by Histone acylation and tighter packing is favored by histone methylation.
- In different cells, different tails have different patterns of modification. The overall pattern of modification causes a change in the activity of the associated DNA known as the Histone code (Set of histone modifications that show whether the chromatin is active or not. These histone codes are read by those proteins involved in the translation of DNA and in gene expression.
- Histone Acetylation and De-acetylation– The tails are made up of specific amino acids, the addition of the acetyl group (Acetylation) to the chain of the amino acids is carried out by an enzyme Histone acetyltransferase (HAT) which causes the chromatin de-condensation, reduces the positive charge and interactions of histones with DNA become weak. It also makes the DNA more accessible to RNA polymerase II and thus facilitates the process of transcription. Similarly, when we remove the acetyl group it suppresses the transcription.
- Histone Methylation-The methylation of amino acid lysine is carried out by Histone methyl transferase (HMT). For example Methylation of fourth lysine (H3K4) in histone H3 indicates the genes are active while methylation of lysine at the 9 and 27 positions indicates the gene is inactive. Methylation is unable to neutralize the charge but it can suppress the regulatory proteins that perform the function of binding methylated histones.