Epigenetics

Epigenetics (Greek: after, behind, around, in addition) refers to processes in a cell that are considered "additional" to the processes of genetics. In contrast to the term "gene regulation", epigenetics defines all meiotically and mitotically heritable changes in gene expression that are not encoded in the DNA sequence itself. Epigenetics represents a plausible regulatory link between environmental influences and genome function and is recognized as an important factor in the development of complex diseases. Epigenetic influences help determine under which circumstances which gene is switched on and when it is silenced again (gene regulation).

Epigenetic regulation includes the marking of DNA segments by means of methylation, histone modifications and non-coding micro-RNA (miRNA). DNA methylation is the best-studied epigenetic mechanism to date.

While genetic processes take many generations to become established, the epigenome can change rapidly in response to environmental stimuli. These changes can be passed on to the next generation.

The term "epigenesis" is used as an example to describe all gradual processes of embryonic morphogenesis of organs. These are based on epigenetic processes during cell division of the precursor cells, cell differentiation (see below mosaic, cutaneous).

The epigenetic processes include:

• Paramutation
• bookmarking
• imprinting
• gene silencing
• X-inactivation
• positional effects
• maternal effects
• the process of carcinogenesis (see also oncogenesis)
• many effects of teratogenic substances.

Epigenetics and drugs: It is sometimes argued that numerous drugs have epigenetic effects. This is known from certain. Psychotropic drugs such as fluoxetine, as well as morphines. Some of these gene expression adaptations are the result of an altered DNA structure caused by chromatin remodeling of epigenetic modifications.

Epigenetic dysregulation is important for the development of immunological diseases (e.g. studied in systemic lupus erythematosus and atopic dermatitis) and various neurological diseases.

The term epigenetics was coined in 1934 by the Russian biologist Nikolai K. Koltsov (1872-1940), one of the key figures in Russian biology. Koltsov advocated the hypothesis that epigenetic changes influence the expression of chromosomes. In 1942, the British embryologist C. H. Waddington specified the term epigenetics in the sense of epigenesis, parallel to Valentin Haecker's phenogenetics. Waddington recognized that epigenetic mechanisms play an important role in heredity, development and evolution. He understood epigenetics as the sum of factors that act at cell, cell group or embryonic level to enable development, including genetic as well as internal and external environmental factors. He attributed the multitude of genetic alternatives to the fact that many genes are always involved in the formation of a phenotypic trait in combination. Environmental stressors play an important role here, which can affect not only an individual animal, but the entire population. However, the term epigenetics only acquired its current meaning in the 1990s. In 1953, Waddington provided empirical evidence for his theories in the article "Genetic Assimilation of an Acquired Character", where he shows how the veins in fly wings disappear, triggered by repeated short heat shocks to the fly eggs over several generations, and how the veins eventually disappear in some animals even without the heat shocks. The change is assimilated in the development of the flies. The very short-term evolution of the beak shapes of Darwin's finches, as described by Peter and Rosemary Grant after Darwin, is also associated with developmental changes, especially with changes in the Hsp90 protein.

The term epigenetics is used by scientists to describe heritable characteristics of cells that are not fixed in the sequence of DNA building blocks. With the complete decoding of the human genome, it has become increasingly clear that many more factors regulate the functions of the human body than genes alone. Proteins, which regulate how accessible individual genes are, play a huge role in the function of genes. There are also chemical changes to the genetic building blocks themselves, which provide them with additional "epigenetic" information. Together, these epigenetic modifications determine which genes are switched on and off when and where and how cells implement their specific genetic programs. Knowledge of these epigenetic marks should provide information on how lifestyle, for example diet, changes certain gene functions in affected cells.

Bees provide an example of how food alone can have an epigenetic effect. Bee larvae that receive a honey-pollen mash become sterile worker bees. The larva that receives royal jelly becomes a queen. It has now been discovered why this is the case: the honey-pollen mash ensures that genes for bee development are extraordinarily methylated and thus silenced. Conversely, the royal jelly contains up to five percent of a fatty acid that can epigenetically reactivate silenced genes.

A definition of the term "epigenetic trait" as a "stably heritable phenotype resulting from changes to a chromosome without changes to the DNA sequence" was formulated at a conference in Cold Spring Harbor in 2008.

1. DeVries A et al(2015) Early predictors of asthma and allergy in children: the role of epigenetics. Curr Opin Allergy Clin Immunol 15:435-439.
2. Guo Y et al(2014) Epigenetics in the treatment of systemic lupus erythematosus: Potential clinical application.Clin Immunoldoi: 10.1016/j.clim.2014.09.002.
3. Kabesch M (2014) Epigenetics in asthma and allergy Curr Opin Allergy Clin Immunol 14:62-68.