Epigenetics

Epigenetics is the study of heritable phenotypic modifications that do not entail DNA sequence changes in biology. [1Epigenetics is defined by features that are “on top of” or “in addition to” the usual genetic foundation for heredity. The Greek prefix epi- (- “over, outside of, surrounding”) denotes traits that are “on top of” or “in addition to” the traditional genetic basis for inheritance. Modifications in gene activity and expression are the most common epigenetic changes, although the phrase can also refer to any heritable phenotypic change. External or environmental influences may have an effect on cellular and physiological phenotypic features, or they may be a normal aspect of development.

Molecular basis

Epigenetic changes modify the activation of certain genes, but not the genetic code sequence of DNA. The microstructure (not code) of DNA itself or the associated chromatin proteins may be modified, causing activation or silencing. This mechanism enables differentiated cells in a multicellular organism to express only the genes that are necessary for their own activity. Epigenetic changes are preserved when cells divide. Most epigenetic changes only occur within the course of one individual organism’s lifetime; however, these epigenetic changes can be transmitted to the organism’s offspring through a process called transgenerational epigenetic inheritance. Moreover, if gene inactivation occurs in a sperm or egg cell that results in fertilization, this epigenetic modification may also be transferred to the next generation.

Specific epigenetic processes include paramutationbookmarkingimprintinggene silencingX chromosome inactivationposition effectDNA methylation reprogrammingtransvectionmaternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning.

DNA damage

DNA damage can also cause epigenetic changes. DNA damage is very frequent, occurring on average about 60,000 times a day per cell of the human body (see DNA damage (naturally occurring)). These damages are largely repaired, but at the site of a DNA repair, epigenetic changes can remain. In particular, a double strand break in DNA can initiate unprogrammed epigenetic gene silencing both by causing DNA methylation as well as by promoting silencing types of histone modifications (chromatin remodeling – see next section). In addition, the enzyme Parp1 (poly(ADP)-ribose polymerase) and its product poly(ADP)-ribose (PAR) accumulate at sites of DNA damage as part of a repair process. This accumulation, in turn, directs recruitment and activation of the chromatin remodeling protein ALC1 that can cause nucleosome remodeling. Nucleosome remodeling has been found to cause, for instance, epigenetic silencing of DNA repair gene MLH1. DNA damaging chemicals, such as benzenehydroquinonestyrenecarbon tetrachloride and trichloroethylene, cause considerable hypomethylation of DNA, some through the activation of oxidative stress pathways.

Foods are known to alter the epigenetics of rats on different diets.Some food components epigenetically increase the levels of DNA repair enzymes such as MGMT and MLH1and p53.Other food components can reduce DNA damage, such as soy isoflavones. In one study, markers for oxidative stress, such as modified nucleotides that can result from DNA damage, were decreased by a 3-week diet supplemented with soy. A decrease in oxidative DNA damage was also observed 2 h after consumption of anthocyanin-rich bilberry (Vaccinium myrtillius L.) pomace extract.

Techniques used to study epigenetics

Epigenetic research uses a wide range of molecular biological techniques to further understanding of epigenetic phenomena, including chromatin immunoprecipitation (together with its large-scale variants ChIP-on-chip and ChIP-Seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase identification (DamID) and bisulfite sequencing. Furthermore, the use of bioinformatics methods has a role in computational epigenetics.

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