What are Histone Proteins?
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 around histones in order to fit inside the nucleus and participate in chromosome formation.
Histones are basic proteins with positive charges that allow them to bind to negatively charged DNA. There are some histones that act as spools around which the thread-like DNA wraps.
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.
Types of Histones
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There are five types of histones that have been identified: H1 (or H5), H2A, H2B, H3 and H4, the core histones are H2A, H2B, H3, and H4, and the linker histones are H1 and H5. H1 as well as its homologous protein H5 are involved in higher-order chromatin structures. The other four types of histones form nucleosomes when they bind to DNA. H1 (or H5) has about 220 residues. Other types of histones are smaller, with 100-150 residues.
Histone H2A
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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 are distinguished primarily by 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
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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.
What is Histone Acetylation?
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Histone acetylation is an epigenetic modification that is unmistakably linked to increased gene transcription proclivity. Because gene transcription is a key component of long-term memories, increases in histone acetylation generally favour learning and memory and can be regarded as molecular memory aids.
In terms of neuronal depolarization and synaptic plasticity, histone acetylation readily responds to neuronal activity. So far, two pathways have been identified as mediating this response: the mitogen-activated protein kinase (MAPK) pathway and the dissociation of histone deacetylase 2 (HDAC2) from chromatin.
Histone Modification
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Histone modifications either directly (e.g., acetyl groups that repel negatively charged DNA to create open chromatin conformation) or indirectly (via protein adaptors known as effectors) regulate the physical properties of chromatin and its corresponding transcriptional state.
Effector proteins recognise and bind to specific epigenetic marks, and then recruit molecular machinery to change the structure of chromatin. By translating the histone code into action, these epigenetic readers determine the functional outcome of histone modifications.
Histone Methylation
We can define the term histone methylation as the process by which methyl groups are transferred to the amino acids of histone proteins, and which form nucleosomes around which the DNA double helix wraps to form chromosomes. Depending on which amino acids in the histones are methylated and how many methyl groups are attached, histone methylation can either increase or decrease gene transcription.
Methylation events that weaken the chemical attraction between histone tails and DNA promote transcription by allowing the DNA to uncoil from nucleosomes, allowing transcription factor proteins as well as RNA polymerase to access the DNA.
Histone Deacetylase
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Histone deacetylases can be defined as a type of enzyme that removes acetyl groups from a histone's -N-acetyl lysine amino acid, allowing the histones to wrap the DNA more tightly. This is significant because DNA is wrapped around histones, and acetylation and deacetylation regulate DNA expression.
What is Nucleoplasmin?
The first protein to be described as a molecular chaperone was nucleoplasmin. Nucleoplasmin research has resulted in advancements in two areas of cell biology.
To begin, the pathway of nucleosome assembly in Xenopus oocytes and eggs has been elucidated, and it is the only assembly pathway that is known in detail. Nucleosome assembly generally represents the major chaperoning function of nucleoplasmin.
Second, nucleoplasmin was used to study protein transport into the nucleus, revealing a selective entry mechanism for nuclear proteins, passage through the nuclear pore complex, and a two-step transport mechanism.
FAQs on Histone
1. What are histones and what is their primary function in a cell?
Histones are a family of small, positively charged proteins found in the nucleus of eukaryotic cells. Their primary function is to package and compact the long, negatively charged DNA molecules into a much smaller volume. This organised structure, known as chromatin, not only fits the DNA inside the nucleus but also plays a crucial role in regulating gene expression, DNA replication, and repair. You can learn more about this in the context of the molecular basis of inheritance.
2. What are the main types of histone proteins found in eukaryotes?
There are five major types of histone proteins in most eukaryotic cells. They are categorised into two groups:
- Core Histones: These include H2A, H2B, H3, and H4. Two copies of each of these four histones assemble to form a histone octamer.
- Linker Histone: This is H1, which binds to the DNA strand where it enters and exits the core particle, helping to lock the DNA in place and facilitate further compaction.
3. How do histones and DNA interact to form a nucleosome?
The interaction is based on electrostatic attraction. DNA has a negatively charged phosphate backbone, while histones are rich in positively charged amino acids. Approximately 147 base pairs of DNA wrap around a central core of eight histone proteins (the histone octamer). This fundamental repeating unit of DNA packaging is called a nucleosome, often described as resembling 'beads on a string'.
4. What is a histone octamer?
A histone octamer is the protein complex at the core of a nucleosome. It is composed of eight histone proteins: two molecules each of the core histones H2A, H2B, H3, and H4. This octamer acts as a spool around which the DNA winds, forming the first and most basic level of chromosome condensation in eukaryotic cells.
5. Why are histones positively charged, and what is the significance of this charge?
Histones are positively charged because they have a high proportion of basic amino acids, particularly lysine and arginine. These amino acids have side chains that are positively charged at the cell's physiological pH. The significance of this positive charge is critical: it allows the histones to bind tightly to the negatively charged phosphate backbone of DNA. This electrostatic attraction neutralises the repulsion between DNA strands, enabling DNA to be densely compacted.
6. How do histone modifications like acetylation affect gene expression?
Histone modifications are a key part of epigenetic regulation. Histone acetylation, for example, involves adding an acetyl group to lysine residues on histone tails. This neutralises their positive charge, weakening the interaction between the histones and DNA. As a result, the chromatin structure becomes more relaxed and open (euchromatin), making the DNA accessible to transcription machinery and generally leading to the activation of gene expression. Conversely, deacetylation tightens the chromatin, silencing genes.
7. What is the difference between histones and non-histone proteins?
The main difference between histones and non-histone proteins lies in their function and composition.
- Histones are the main structural proteins that package DNA into nucleosomes. They are relatively few in type (H1, H2A, H2B, H3, H4) and are highly conserved across species.
- Non-histone chromosomal proteins (NHCPs) are a large, diverse group of other proteins associated with chromatin. They are involved in various functions, including DNA replication, transcription regulation, and higher-order chromosome scaffolding.
8. Do all living organisms have histones?
No, histones are a hallmark of eukaryotic cells. Most prokaryotic organisms, like bacteria, lack histones and use a different set of proteins (nucleoid-associated proteins) to compact their circular DNA into a structure called the nucleoid. Interestingly, some Archaea (which are also prokaryotes) possess proteins that are structurally similar to eukaryotic histones. Furthermore, some rare eukaryotes, such as dinoflagellates, do not use histones to package their DNA.
