Histones are proteins involved in packing and structuring DNA in the nucleus of eukaryotic cells. They make up the nucleosome along with DNA. Histones are spools on which DNA is wrapped, and they also regulate genes. These proteins swell DNA into chromatin, a compact molecule that holds genetic data and helps keep it locked and controlled. Dynamic histone modifications, like methylation, are epigenetic signatures that drive gene expression and cell function.
Related Products
Structure and Physiological Functions of Histones
Histones are simple proteins that cling to DNA, found in chromosomes. They're the building blocks of nucleosomes (the building block of chromatin). Histones help chromosomes to form. The histone octamer is made of two copies of histones H2A, H2B, H3, and H4, which enfold around DNA to make nucleosome core particles. The Histone H1 then clings to the connecting DNA fragment to further stabilize the chromatin structure. Among the many biological functions that hitherto were to control genes, replicate DNA, and repair itself are all histones. Histones regulate gene expression by controlling the accessibility of DNA to transcription factors and regulatory proteins, determining which genes are expressed or silenced in cells. Histones also help to hold the genome together and assemble higher-order chromatin.
Fig. 1 Diagram of the structure of histones (Venkatesh, S.; et al. 2015).
Methylation Modification of Histones
Histones are mainly methylated by a group of proteins that are made up of SET domains. The modification of the methylation of histones plays a role in many of the big physiological processes including the creation of heterochromatin, the imprinting of genes, X chromosome degeneration, and transcription. Editing histones is a critical area of epigenetics. Histone methylation is an epigenetic process that alters histone proteins, modulating gene expression and cell function. Methylated by the enzyme Histone, usually at lysine and arginine residues and its regulatory molecular mechanism is like this:
The Role of Enzymes
Histone methylation is controlled by histone methyltransferases (HMTs), which modify histones by binding methyl (-CH3) to particular histone sites. There is substrate specificity and function between enzymes.
The function of methylation sites
There is biological value to different methylation locations. For instance: H3K4 methylation generally corresponds to gene transcriptional activation. Gene silencing relates to methylation of H3K9 and H3K27.
Demethylation
Histone methylation is reversed. Demethylases (histone demethylases, JMJs, LSDs) can demethylate and regulate gene expression.
Regulatory Network
Histone methylation combines with other epigenetic changes (acetylation, phosphorylation, etc.) to jointly regulate gene expression. All of this is a regulatory web.
Diseases Caused by Histone Abnormalities
Histone abnormalities are alterations in histone structure or function that could cause inappropriate gene expression control and many kinds of disorders. Hepatic abnormal histone modifications (methylation, acetylation, phosphorylation) are linked to all manner of diseases:
- Cancer
- Genetic diseases
- Neurological diseases
- Obesity
- Metabolic syndrome
- Cardiovascular disease
Histones Affect Epigenetic Regulation
Histone modification
Histones methylate chromatin and modulate gene expression in a host of chemical ways (acetylation, methylation, phosphorylation, pan-ubiquitination, etc). Such changes change how accessible DNA is and therefore how genes get turned on or off.
Chromatin Remodeling
Histone changes can attract particular protein complexes that participate in chromatin remodelling, pulling DNA looser or tighter, which effects gene accessibility and expression.
Histone Variants
Not only the traditional H2A, H2B, H3, and H4, but also some variant histones (H3.3, CENP-A, etc. ), that play important roles in particular biological activity, coordinate gene expression and keep chromatin in a special condition.
Composition and Function
Histones do more than simply encase segments of DNA; they also play a crucial role in regulating gene expression. Some histone binding factors can also control transcription of genes by binding to transcription factors. So histones are also a very important part of the gene regulatory system.
Genetic and Environmental Interactions
The change of histones might be a signal that the cells have made in response to environmental triggers. Such changes can fix the pattern of expression of genetic information to some degree and thus change the phenotype of the person. It is how epigenetic regulation can modulate gene expression under environmental circumstances.
Conclusion
Histones undergo methylation at specific sites and states through lysine methylation, facilitated by a class of proteins that includes those with the evolutionarily conserved SET domain. Histone methyltransferases research forms part of epigenetics, the basic science behind heterochromatin, X-chromosome inactivation and transcription.
Histones are structures and functions of chromatin, responsible for gene regulation and genome stability. The epigenetic switch, called the methylation of histone, alters the accessibility of chromatin and calls in effector proteins to modulate gene expression. We need to know how histones, histone modifications and gene expression interact to break the puzzle of epigenetic regulation in health and disease.
Non-histone proteins have also been methylated by histone methyltransferases that have SET domains, and its target is probably histones. Research on histone methyltransferases will leave a whole new frontier of transcription, embryology, cell division and signalling.
References
- Roth, S.; et al. Histone acetyltransferases. Annual review of biochemistry 2001, 70(1): 81-120.
- Venkatesh, S.; et al. Histone exchange, chromatin structure and the regulation of transcription. Nature reviews Molecular cell biology 2015, 16(3): 178-189.
.
