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Epigenetics

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Epigenetics is the scientific study of changes in gene expression that do not alter the underlying DNA sequence. The term uses the Greek prefix "epi-", which means "on top of" or "around."

Epigenetic mechanisms
Epigenetic mechanisms

This implies that epigenetic mechanisms act as an additional layer of control above the traditional DNA-based inheritance. These changes affect how genes are regulated and how they are expressed within a cell. Most epigenetic effects can persist through cell division, meaning they are passed from a parent cell to its daughter cells. They may also be part of normal biological development or result from environmental factors.

One of the primary ways cells control gene expression is through chromatin remodeling. DNA does not sit loosely in the cell; it associates with proteins called histones to form a complex called chromatin.

Nucleosome 1KX5 2
Nucleosome 1KX5 2

If the way DNA is wrapped around these histones changes, the cell's ability to read certain genes also changes. This remodeling happens through post-translational modification of the amino acids within the histone proteins. For example, changing the amino acids can alter the shape of the histone. When DNA replicates, these modified histones can be carried into the new DNA copies. They then act as templates to ensure the new histones are shaped in the same way, maintaining a specific cellular program.

Another critical mechanism is DNA methylation. This process involves adding a methyl group to the DNA molecule, most often at sites called CpG sites. This often converts cytosine into 5-methylcytosine.

Cytosine and 5-methylcytosine
Cytosine and 5-methylcytosine

The effect of this modification depends on where it occurs in the genome. When methylation happens in the promoter or enhancer regions of a gene, it often represses that gene. This occurs because about 22% of transcription factors are prevented from binding to their recognition sequences when a methylated cytosine is present. Furthermore, methylated cytosines can attract methyl-CpG-binding domain (MBD) proteins, which lead to gene silencing.

Methylation and histone modification often work together in a reciprocal relationship. For instance, the MBD1 protein is attracted to methylated cytosine at a CpG site. Once attached, MBD1 can associate with methyltransferase activity to methylate histone 3 at lysine 9. This shows how chemical changes on the DNA can directly trigger chemical changes on the proteins surrounding it. Conversely, enzymes called TET enzymes can perform demethylation, which is the removal of these methyl groups. In the human brain, hundreds of such demethylation events occur during processes like learning and memory formation.

Initiation of DNA demethylation at a CpG site
Initiation of DNA demethylation at a CpG site

The history of these ideas spans several centuries. The term "epigenesis" has been used in English since the 17th century to mean "extra growth." In 1942, the British embryologist C. H. Waddington coined the specific term "epigenetics." He used it to describe the relationship between genotypes and phenotypes. Waddington created a famous metaphor called the "epigenetic landscape" to explain how cells develop. He imagined cells as marbles rolling down a landscape of ridges and valleys. This helped visualize how cell fates become established during development through a process he called canalisation.

EpigenByYear 1
EpigenByYear 1

Scientific definitions of epigenetics have evolved significantly over time. In 1990, Robin Holliday defined it as the study of temporal and spatial control of gene activity. Later, researchers like Arthur Riggs provided a stricter definition involving changes that are mitotically or meiotically heritable. In 2008, a consensus definition was reached at a Cold Spring Harbor meeting. This definition described an epigenetic trait as a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence." Other scientists, such as Adrian Bird, have proposed broader definitions that include transient modifications used during DNA repair.

Brain regions in memory formation updated
Brain regions in memory formation updated

Epigenetics is essential for a process called cellular differentiation. This is how a single fertilized egg, known as a zygote, develops into a complex organism. During morphogenesis, totipotent stem cells become pluripotent cell lines, which eventually become fully differentiated cells. By activating some genes and inhibiting others, these cells turn into specialized types like neurons, muscle cells, or the endothelium of blood vessels. This entire system is often referred to as the "epigenetic code." This code represents the set of features that allow cells with the exact same DNA to have completely different functions and identities.

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🖼️ Images & Media (7)
File:Epigenetic mechanisms.png
Epigenetic mechanisms.png
File:EpigenByYear 1.png
EpigenByYear 1.png
File:Nucleosome 1KX5 2.png
Nucleosome 1KX5 2.png
File:Initiation of DNA demethylation at a CpG site.svg
Initiation of DNA demethylation at a CpG site.svg
File:Brain regions in memory formation updated.jpg
Brain regions in memory formation updated.jpg
File:Cytosine and 5-methylcytosine.svg
Cytosine and 5-methylcytosine.svg
File:Escherichia coli flagella TEM.png
Escherichia coli flagella TEM.png
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