Epigenetics
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The term epigenetics has over time been used in various senses, in part because the Greek prefix epi- has at least six meanings in English (including 'on', 'after' and 'in addition'), but also because various theories of epigenetic development, inheritance, and evolution have been proposed (see Historical notes below).
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The modern view
In biology today, epigenetics has two closely related meanings:
- The study of the processes involved in the unfolding development of an organism. This includes phenomena such as X chromosome inactivation in mammalian females, and gene silencing within an organism.
- The study of heritable changes in gene function that occur without a change in the sequence of nuclear DNA. This includes the study of how environmental factors affecting a parent can result in changes in the way genes are expressed in the offspring (see Waterland citation).
In both cases, the object of study includes how gene regulatory information that is not expressed in DNA sequences is transmitted from one generation (of cells or organisms) to the next - that is (harking back to the Greek prefix), 'in addition to' the genetic information encoded in the DNA.
In recent years, there has been rapid progress in understanding epigenetic mechanisms, which include differences in DNA methylation, as well as difference in chromatin structure. Another possibility involves the genomes of cytoplasmic elements (chloroplasts and mitochondria). Other mechanisms have also been proposed. See epigenetic inheritance for a more detailed discussion.
The epigenome is the overall epigenetic state of a cell. As one embryo can generate a multitude of cell fates during development, one genome could be said to give rise to many epigenomes.
One way a gene can be expressed is through the acetylation on the K9 and K4 lysines of the N-terminus tails of the internal histones of the nucleosome. Since lysine normally has a positive charge on the nitrogen at its end it can bind the negitively charged phosphates of the DNA backbone and prevent them from repelling each other. When the charge is neutralized the DNA can fold tightly thus preventing access to the DNA by the transcriptional machinery. When an acetyl group is added to the +NH2 of the lysine it removes the positive charge and causes the DNA to repel itself and not fold up so tightly. When this occurs, complexes like SWI/SNF and other transcriptional factors can bind to the DNA and open it up to expose it to enzymes like RNA polymerase so transcription of the gene can occur.
Historical notes
Some biologists at one time believed that genetics, which seemed to postulate a one-to-one correspondence between genotype and phenotype, could not explain cell differentiation. They developed a theory that each undifferentiated cell underwent a crisis that determined its fate, which was not inherent in its genes, and was therefore (borrowing from the Greek) epigenetic.
The psychologist Erik Erikson developed an epigenetic theory of human development which focuses on psycho-social crises. In Erikson's view, each individual goes through several developmental stages, the transition between each of which is marked by a crisis. According to the theory, although the stages are largely predetermined by genetics, the manner in which the crises are resolved is not; by analogy with the epigenetic theory of cell differentiation, the process was said to be epigenetic.
The biologist C.H. Waddington is sometimes credited with coining the term epigenetics in 1942, when he defined it as “the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being”. However the term goes back at least to 1896 (see References).
Various aspects of the modern understanding of epigenetic inheritance are reminiscent of Jean-Baptiste Lamarck's ideas about evolution.
See also
References
- Oscar Hertwig, 1849-1922. "Biological problem of today: preformation or epigenesis? The basis of a theory of organic development". W. Heinemann: London, 1896.
- Eva Jablonka and Marion J. Lamb. The Changing Concept of Epigenetics. Annals of the New York Academy of Sciences 981:82-96 (2002).
- Joshua Lederberg, "The Meaning of Epigenetics", The Scientist 15(18):6, Sep. 17, 2001.
- C.H. Waddington (1942), "The epigenotype" Endeavour 1, 18–20.
- R.A. Waterland, R.L. Jirtle, "Transposable elements: Targets for early nutritional effects on epigenetic gene regulation", Molecular and Cellular Biology 2003 August 1;23(15):5293-5300.nl:Epigenetica