Epigenetics

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For the unfolding of an organism or the theory that plants and animals (including humans) develop in this way, see epigenesis (biology). For epigenetics in robotics, see developmental robotics.

In biology, and specifically genetics, epigenetics is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence; it also can be used to describe the study of stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. Unlike simple genetics based on changes to the DNA sequence (the genotype), the changes in gene expression or cellular phenotype of epigenetics have other causes. The name epi- (Greek: επί- over, outside of, around) -genetics.^[1]

 

The term also refers to the changes themselves: functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations even though they do not involve changes in the underlying DNA sequence of the organism;^[2] instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.^[3] (There are objections to the use of the term epigenetic to describe chemical modification of histone, since it remains unclear whether or not histone modifications are heritable.)^[4]

 

One example of an epigenetic change in eukaryotic biology is the process of cellular differentiation. During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo, which in turn become fully differentiated cells. In other words, as a single fertilized egg cell – the zygote – continues to divide, the resulting daughter cells change into all the different cell types in an organism, including neurons, muscle cells, epithelium, endothelium of blood vessels, etc., by activating some genes while inhibiting the expression of others.^[5]

 

In 2011, it was demonstrated that the methylation of mRNA plays a critical role in human energy homeostasis. The obesity-associated FTO gene is shown to be able to demethylate N6-methyladenosine in RNA. This discovery launched the subfield of RNA epigenetics.^[6][7]

Molecular basis of epigenetics

Epigenetic changes can modify the activation of certain genes, but not the sequence of DNA. Additionally, the chromatin proteins associated with DNA may be activated or silenced. This is why the differentiated cells in a multi-cellular organism 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, but, if gene inactivation occurs in a sperm or egg cell that results in fertilization, then some epigenetic changes can be transferred to the next generation.^[22] This raises the question of whether or not epigenetic changes in an organism can alter the basic structure of its DNA (see Evolution, below), a form of Lamarckism.

 

Specific epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning.

 

DNA damage can also cause epigenetic changes.^[23][24][25] DNA damages are very frequent, occurring on average about 10,000 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.^[26] 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).^[27] 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.^[28] This accumulation, in turn, directs recruitment and activation of the chromatin remodeling protein ALC1 that can cause nucleosome remodeling.^[29] Nucleosome remodeling has been found to cause, for instance, epigenetic silencing of DNA repair gene MLH1.^[19][30] DNA damaging chemicals, such as benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene, cause considerable hypomethylation of DNA, some through the activation of oxidative stress pathways.^[31]

 

Foods are known to alter the epigenetics of rats on different diets.^[32] Some food components epigenetically increase the levels of DNA repair enzymes such as MGMT and MLH1^[33] and p53.^[34][35] Other food components can reduce DNA damage, such as soy isoflavones^[36][37] and bilberry anthocyanins.^[38]

 

^{For more details and references see http://en.wikipedia.org/wiki/Epigenetics}