The human body is composed of over 200 different cell types, with diverse functions and morphologies. Yet paradoxically, in spite of this diversity, every individual cell has more or less the same genetic material to work with. The variety in shape and form is due to every cell using their genomes differently, choosing which genes should be turned on/off, when, and to what degree. The regulatory layer, which governs the behaviour of the genome was eventually coined as epigenome, and the study of this regulatory layer was defined as epigenetics [1,2].
The term epigenetics literally refers to “on top of or in addition to genetics.” It distinguishes itself from typical genetics because, unlike genetics, some of its changes are reversible and most importantly, it does not change the DNA sequence. Instead, it informs how the machinery of cells read and use this DNA sequence. In addition, molecular and chemical cues from the cellular, extracellular, and physical environment can all shape the manner in which the epigenome works. This makes the epigenome highly dynamic and flexible [3].
Epigenetic changes that modulate gene expression fall into three different categories:
Histone Modifications
DNA within the nucleus of cells is wound around proteins known as the histones. The winding of DNA around these histones allow for the tight packaging of the long DNA molecule within the tiny nuclei of cells. These histones can be chemically modified by proteins to instruct how DNA wound around them can be used. Some modifications turn genes on by causing them to be loosely wound around the histone octamers (called like this because it’s an eight protein complex), making them more accessible to the replication machinery (more information here); whereas others can turn genes off by tightly wrapping them around histone octamers.
DNA Methylation
DNA can also be directly marked with a chemical mark known as methylation. Although this molecule is small, this methylation mark informs the cell that this region of the genome should be repressed, therefore any genes marked will be turned off.
RNA Silencing
RNA can also be used to suppress or silence the activity of genes. Small non-coding (does not produce proteins) RNAs known as microRNAs (miRNA) bind to the transcript of genes and trigger their premature degradation. One paper found that miRNAs represent only 1% of the human genome, yet they target 30% of genes [5].
If you want to learn about why it is important to study the mechanisms of epigenetics, stay tuned for next week’s post about its applications!
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Written by: Renard
Edited by: María and Natasha
BioDecoded is a volunteer group committed to sharing accurate scientific information. For more information about vaccines and their safety profile, please see previous posts or consult with your personal physician. If you have any questions about this topic, please comment or send them to our email.
References:
1. Rivera, C., et al. (2013) “Mapping human epigenomics”, Cell 155, 39-55. Available at: https://www.cell.com/action/showPdf?pii=S0092-8674%2813%2901148-3
2. “What is epigenetics” (2022), CDC. Available at: https://www.cdc.gov/genomics/disease/epigenetics.htm#:~:text=Epigenetics%20is%20the%20study%20of,body%20reads%20a%20DNA%20sequence (Accessed June 13 2022)
3. Kanherkar, R., et al. (2014) “Epigenetics across the human lifespan”, Frontiers in Cell and Developmental Biology, 2. Available at: https://www.frontiersin.org/articles/10.3389/fcell.2014.00049/full
4. He, H. et al. (2018) “The tale of histone modifications and its role in multiple sclerosis”, Human Genomics, 12(1). Available at: https://humgenomics.biomedcentral.com/articles/10.1186/s40246-018-0163-5/figures/1
5. Lewis, B P., et al. (2005) “Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets”, Cell 120 (1), 15-20. Available at: https://www.cell.com/cell/fulltext/S0092-8674(04)01260-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867404012607%3Fshowall%3Dtrue
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