Histones: Types, Functions and Sample Questions

Histones are a type of basic protein that binds to DNA in the nucleus and helps it condense into chromatin. Nuclear DNA does not exist in free linear strands. It is highly condensed and wrapped in structure around histones in order to fit inside the nucleus and participate in chromosome formation. DNA is highly condensed and is wrapped around histones in eukaryotes to form chromatin thread, which results in the formation of chromosomes. Histones give a structural framework to chromosomes. Here, we will be learning more about hostones, its types, modification and discussing some important questions. 

Key takeaways: Histones, Chromosomes, Chromatin Fibres, DNA, proteins

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Types of Histones

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Chromatin appears as beads on a string under the microscope in its expanded form. The beads are known as nucleosomes. Each nucleosome is made up of eight histone proteins that act like spools and are known as histone octamers. Each histone octamer contains two copies of each histone protein H2A, H2B, H3, and H4. The nucleosome chain is then wrapped into a 30 nm spiral known as a solenoid, where additional H1 histone proteins are associated with each nucleosome to maintain chromosome structure.

Histone H2A

Many of the fancy tail modifications that have made H3 and H4 so popular in epigenetics may not be present in H2A. H2A has the most variants, resulting in a dizzying array of nucleosome composition diversity. H2A variants differ primarily in their C-terminus, which is responsible for intra-nucleosome and DNA binding. The acidic patch, which is involved in higher order chromatin organisation, is also altered between variants.

Histone H2B 

H2B forms a tetramer with (H2A-H2B)-2. In comparison to H3 and H4, this tetramer and its component dimers are easily exchanged in and out of the nucleosome, implying that the modifications on H2A and H2B are less likely to be maintained in chromatin.

Histone H3KA

When you think of H3K4, you think of activation. This site, whether methylated or acetylated, will turn genes faster than you can say PRDM9. Acylation of all histone residues, including H3K4, is activating. The real fascination with H3K4 is in its methylation.

Histone H3K9

H3K9 serves two functions. It can activate genes when acetylated, but it can also silence them when methylated. H3K9ac is a particularly important acetylation because it is strongly associated with active promoters. H3K9ac has a high co-occurrence with H3K14ac and H3K4me3, and these three marks, when combined, are the hallmark of active gene promoters.

Histone H3K27L

H3K27 is well-known for one thing: it inhibits transcription. When H3K27 is trimethylated, it is strongly linked to inactive gene promoters. It works in the opposite direction of H3K4me3. H3K27me3 is a favourite of epigeneticists looking for inactive genes due to its dramatic and predictable effect on gene expression.

Histone H3K36

H3K36 is like a fine wine: complex, intriguing, and a constant source of research interest. The changes that occur at H3K36 are extremely diverse and bear little resemblance to one another. They play important roles in a variety of biological processes.

Histone H4K5

H4K5 is the lysine residue closest to histone H4's N-terminal tail. Histone H4 and histone H3 form a strong tetramer. H4, like histone H3, has a long N-terminal tail that is subject to a variety of acetylations and methylations that are involved in a variety of cellular processes. H4 modifications are not as well defined as H3 modifications. H4 has much less sequence variation across species than the other histones; it appears to be structurally restrained by evolution, most likely due to its important function.

Histone H4K8

H4K8 is a lysine on the tail of histone H4 that receives little attention. It, like the others in this group, has only been shown to be acetylated; it has not yet been shown to be methylated. This lysine group is known to act as transcriptional activators. These lysines are also a great example of the histone code hypothesis at work.

Histone H4K12

H4K12 is yet another lysine on the N-terminal tail of histone H4 that yet again is acetylated and not methylated. Starting to sound familiar? Like H4K8ac, H4K12ac is part of a “backbone” of histone modifications that are associated with active promoters. H4K12ac is localized to the promoter, like other H4 acetylations; however, H4 localizes more to gene bodies than the other acetylations. This suggests that H4K8ac serves to facilitate transcriptional elongation.

Histone H4K16

H4K16 is a member of what should now be a well-known group of lysines in histone H4's N-terminal tail. If you've been reading about the others, you'll notice that H4K16 is also acetylated rather than methylated. But wait; H4K16ac has some interesting and unique properties. H4K16ac is linked to transcriptional activation, but it can also be linked to repression. TIP5's bromodomain, which is part of NoRC, binds to H4K16ac. After binding, the NoRC complex recruits HATs and DNMTs to silence rDNA.

Histone H4K20

H4K20 is unquestionably the odd lysine on the tail of H4. Up until this point, all of the lysines have been acetylated rather than methylated. H4K20 defies convention by being methylated but not acetylated. H4K20, like all lysine residues, can be mono-, di-, or trimethylated. These methylation states have different spatial disruptions and functions in the case of H4K20.

Also read: Difference Between DNA and RNA

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Functions of Histones

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Histone has an integral role in organizing and packaging of DNA inside the nucleus. They also appear to regulate the expression of genes.

• They basically help in compacting DNA strands into chromosomes, and they form the core around which DNA is wrapped around.
• Histones show post-translational modifications, where they regulate the interaction between DNA and nuclear proteins. Also, they regulate gene expression, condensation during mitosis, spermatogenesis, DNA repair, etc.
• Histone modifications prevent DNA damage as well as protect from the UV radiations of the sun.

Also read: Recombinant DNA Technology

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Points to Remember

• A histone is a protein that acts as a structural support for chromosomes. Each chromosome contains a long molecule of DNA that must fit into the nucleus of the cell. To accomplish this, the DNA wraps around complexes of histone proteins, resulting in a more compact shape for the chromosome. 
• Histones also play a role in gene expression regulation.
• Albrecht Kossel discovered histones in avian red blood cell nuclei around 1884. 
• Histones are water-soluble and contain a high concentration of basic amino acids, particularly lysine and arginine. They are particularly abundant in the thymus and pancreas.
• In its expanded form, chromatin appears as beads on a string under a microscope. The beads are referred to as nucleosomes. Each nucleosome is composed of eight histone proteins that act as spools and are referred to as histone octamers. 
• Each histone octamer has two copies of each histone protein (H2A, H2B, H3, and H4). 
• The nucleosome chain is then wrapped into a solenoid, a 30 nm spiral in which additional H1 histone proteins are associated with each nucleosome to maintain chromosome structure.

Also Read: Difference Between Gene and DNA