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Epigenetics

For other uses, see Epigenetic (disambiguation).

Epigenetic mechanisms

In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence.[1] The Greek prefix epi- (ἐπι- "over, outside of, around") in epigenetics implies features that are "on top of" or "in addition to" the traditional (DNA sequence based) genetic mechanism of inheritance.[2] Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression.[3] Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. Epigenetic factors can also lead to cancer.[4]

The term also refers to the mechanism of changes: functionally relevant alterations to the genome that do not involve mutation of 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.[5] Further, non-coding RNA sequences have been shown to play a key role in the regulation of gene expression.[6] 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;[7] instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.[8]

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.[9]

  1. ^ Dupont C, Armant DR, Brenner CA (September 2009). "Epigenetics: definition, mechanisms and clinical perspective". Seminars in Reproductive Medicine. 27 (5): 351–7. doi:10.1055/s-0029-1237423. PMC 2791696. PMID 19711245. In the original sense of this definition, epigenetics referred to all molecular pathways modulating the expression of a genotype into a particular phenotype. Over the following years, with the rapid growth of genetics, the meaning of the word has gradually narrowed. Epigenetics has been defined and today is generally accepted as 'the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence.'
  2. ^ Rutherford A (19 July 2015). "Beware the pseudo gene genies". The Guardian.
  3. ^ Deans C, Maggert KA (April 2015). "What do you mean, "epigenetic"?". Genetics. 199 (4): 887–896. doi:10.1534/genetics.114.173492. PMC 4391566. PMID 25855649.
  4. ^ Sharma S, Kelly TK, Jones PA (January 2010). "Epigenetics in cancer". Carcinogenesis. 31 (1): 27–36. doi:10.1093/carcin/bgp220. PMC 2802667. PMID 19752007.
  5. ^ Kanwal R, Gupta S (April 2012). "Epigenetic modifications in cancer". Clinical Genetics. 81 (4): 303–311. doi:10.1111/j.1399-0004.2011.01809.x. PMC 3590802. PMID 22082348.
  6. ^ Frías-Lasserre D, Villagra CA (2017). "The Importance of ncRNAs as Epigenetic Mechanisms in Phenotypic Variation and Organic Evolution". Frontiers in Microbiology. 8: 2483. doi:10.3389/fmicb.2017.02483. PMC 5744636. PMID 29312192.
  7. ^ Bird A (May 2007). "Perceptions of epigenetics". Nature. 447 (7143): 396–398. Bibcode:2007Natur.447..396B. doi:10.1038/nature05913. PMID 17522671. S2CID 4357965.
  8. ^ Hunter P (1 May 2008). "What genes remember". Prospect Magazine. Archived from the original on 1 May 2008. Retrieved 26 July 2012.
  9. ^ Reik W (May 2007). "Stability and flexibility of epigenetic gene regulation in mammalian development". Nature. 447 (7143): 425–32. Bibcode:2007Natur.447..425R. doi:10.1038/nature05918. PMID 17522676. S2CID 11794102.

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