Last updated on December 27, 2022 by
Do you know that each diploid cell in our body contains around 2 meters of DNA? Then, how does it reside in a 100 μm small cell?
The answer is proteins that compact the DNA into the microscopic space of the eukaryotic nucleus. They are known as histone proteins.
By definition, histones are small, positively charged proteins found in chromosomes. They are abundant in lysine and arginine amino acid residues. They help give chromosomes a proper structure and shape and facilitate gene expression and transcription.
The resulting complex due to histone and DNA interaction is called chromatin. The chromatin in a cell’s nucleus is of two types: heterochromatin, which is associated with transcriptional repression, and euchromatin, associated with transcriptional activation.
Under a microscope, the chromatin structure looks like beads on a string. These beads are known as nucleosomes, which are structures composed of DNA wrapped around eight histone proteins (called histone octamer). Each histone octamer is made of two copies of each protein: histone H2A, histone H2B, histone H3, and histone H4.
The nucleosome is further wrapped around a 30nm spiral called a solenoid into which additional H1 histone proteins (act as linker histone) are attached to maintain the structure of the chromosomes.
There are also some other histone variants, known as minor histones, that have crucial roles in specific chromatin metabolism. Its examples are:
- Histone H3-like CENPA: It’s only associated with the centromere region of the chromosome
- Histone H2A variant H2A.Z: It’s associated with the promoters of actively transcribed genes. Additionally, it also prevents the spread of silent heterochromatin and has a role in genome stability.
- H2A variant H2A.X: It marks the DNA repair region by phosphorylating S139 in regions around double-strand breaks.
- Histone H3.3: It’s associated with the body of actively transcribed genes.
In this article, we will teach you the working mechanism of histone, its functions, and applications in different lab workflows.
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How Does Histone Work?
Histone proteins package DNA into a nucleosome structure. It mainly consists of basic lysine and arginine residues and has N-terminals that are involved in the post-translational modifications (PTMS). The combination of these modifications is known as histone code, which differs from genomic code encoded by DNA sequence.
The N-terminal histone tails provide more surface area for chemical modifications, which are responsible for chromatin remodeling, gene regulation, and transcriptional activation/deactivation. The information is accessed during development and differentiation in distinct cells.
An active gene has fewer bound histones, whereas an inactive gene has many bound histones during the interphase of the cell cycle. The structure of histones also appears to have been conserved evolutionarily, since any deleterious mutation would be severely detrimental.
Histones are modified by enzymes such as histone deacetylases, kinases, histone acetyltransferases, and histone methyltransferases, that regulate gene transcription. Some most common modifications include:
- Methylation: The process of adding methyl groups to histone. Methylation of lysine and arginine residue is the most common type of histone modification. It affects how proteins, like transcription factors, interact with nucleosomes. Histone methylation has a major role in transcriptional activation or repression, based on which lysine residue is methylated. Transcriptional silencing mainly occurs due to high levels of DNA methylation.
- Phosphorylation: The process of adding a phosphate group to a serine residue of histone. Based on the type of modified histone, the DNA can be open or condensed and active or inactive.
- Acetylation: Adding an acetyl group to histones is known as acetylation. It’s facilitated by the enzyme histone acetyltransferases (HATs). Acetylation of lysine residue is one of the most common histone modifications which lead to transcriptional activation and gene expression. The modified histone can be reversed by histone deacetylases (HDACs).
Some other post-translational modifications include citrullination, SUMOylation, ubiquitination, and ADP-ribosylation.
What is Histone Used For?
Histone has a range of functions in organisms. Thus, they are widely used for in vivo and in vitro workflows to study mammalian development or functional characteristics of any other organisms.
DNA is compacted inside cells using histone and non-histone proteins. It’s necessary to fit the large genome of organisms in the nucleus. The compaction level of this dynamic fiber decides access to DNA regions for essential cellular processes, such as replication, transcription, recombination, and repair.
Gene Activity Control
Post-translational modification of histone has a vital role in DNA repair, gene regulation, spermatogenesis (meiosis), and chromosome condensation (mitosis). Gene activity is controlled based on the type of modified histone’s amino acid residue.
For example, trimethylation of H3 lysine 4 (H3K4me3) at the promoter region causes gene activation in the human genome. However, trimethylation of H3 lysine 27 (H3K27me3) acts as an inhibitor of gene activity.
What Industries Use Histone?
Histone has many roles in organisms ranging from untangling DNA and preventing DNA damage to DNA replications and gene regulation. And, because of its extensive roles, it has a spectrum of in vivo and in vitro applications.
Histone modification is one of the most common studies in life sciences labs to understand the activation/deactivation of genes. These types of changes that alter gene activity without changing the DNA sequence or genome of the organism are known as epigenetics. An epigenetic modification technique must contain both a DNA binding molecule and an active epigenetic modification molecule.
Furthermore, histones are also used for the transposition of native chromatin, which facilitates the study of DNA-binding proteins, epigenomic profiling of open chromatin, and nucleosome positions.
Histone modification or epigenetic mechanisms, such as histone acetylation/deacetylation (HDAC), play a crucial role in regulating epithelial-to-mesenchymal transition (EMT) or fibrosis. Further, epigenetics affects various diseases, such as neurodegenerative disorders and cancer. Therefore, the personalization of medicine can be enhanced by epigenetic and drug management data obtained from disease patients.
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Histone is a basic protein abundant in arginine and lysine residue and found in the nucleus of eukaryotic cells. The protein helps in the compaction of DNA inside the nucleus, which keeps the nucleic acid untangled and protects it from damage.
The four types of histones are H1, H2A, H3, and H4. These histone and their N-terminal tails are modified in different ways which determine the activation or deactivation of genes. Some most common post translations modifications (PTMs) of histones include phosphorylation, acetylation, and methylation.
Due to their extensive role in cellular processes, histones have a range of applications in epigenetics, biochemistry, and pharmaceutical workflows. These experiments require scientists to use high-quality reagents paired with high-tech equipment.
But, there’s a way to reduce the cost associated with such high-throughput assays: By using Excedr’s leasing solution.
Excedr allows labs of all sizes, whether beginner or giant, to procure equipment on the lease without paying expensive upfront costs. Further, there’s no stress of paying extra repair and maintenance cost associated with equipment because it’s all covered under our leasing program.
The range of equipment that you can lease from Excedr includes analytical equipment, clinical equipment, and life sciences equipment. All instruments are delivered to the doorstep and installed, and lab personnel is trained to operate them smoothly.
Excedr’s leasing program provides you the flexibility of using your money, saving it for your crucial lab operations, spending more time on your breakthrough experiment, and focusing on earning the compliances you require for your lab. Excedr can help your lab get the technology and equipment it deserves. With the right equipment, you can accelerate your R&D and achieve milestones faster! Get your customized leasing solution now.