Biopolym. Cell. 2014; 30(1):3-9.
http://dx.doi.org/10.7124/bc.000873
Reviews
Epigenetics: What it is about?
1Saade E., 2Ogryzko V. V.
  1. Faculty of Public Health, Lebanese University
    P.O. Box 6573/14 Badaro, Museum, Beirut, Lebanon
  2. CNRS UMR 8126, Universit Paris-Sud 11, Institut Gustave Roussy
    114, rue Edouard Vaillant, Villejuif, France, 94805

Abstract

Epigenetics has captured the attention of scientists in the past decades, yet its scope has been continuously changing. In this paper, we give an overview on how and why its definition has evolved and suggest several clarification on the concepts used in this field. Waddington coined the term in 1942 to describe genes interaction with each other and with their environment and insisted on dissociating these events from development. Then, Holliday and others argued that epigenetic phenomena are characterized by their heritability. However, differentiated cells can maintain their phenotypes for decades without undergoing division, which points out the limitation of the «heritability» criterion for a particular phenomenon to qualify as epigenetic. «Epigenetic stability» encompasses traits preservation in both dividing and non dividing cells. Likewise, the use of the term «epigenetic regulation» has been misleading as it overlaps with «regulation of gene expression», whereas «epigenetic information» clearly distinguishes epigenetic from genetic phenomena. Consequently, how could epigenetic information be transmitted and perpetuated? The term «epigenetic templating» has been proposed to refer to a general mechanism of perpetuation of epigenetic information that is based on the preferential activity of enzymes that deposit a particular epigenetic mark on macromolecular complexes already containing the same mark. Another issue that we address is the role of epigenetic information. Not only it is important in allowing alternative interpretations of genetic information, but it appears to be important in protecting the genome, as can be illustrated by bacterial endonucleases that targets non methylated DNA – i. e. foreign DNA – and not the endogenous methylated DNA.
Keywords: chromatin, heritability, central Dogma, DNA methylation, genetic switch, evolution
Full text: (PDF, in English)

References

[1] Gurdon JB, Elsdale TR, Fischberg M. Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature. 1958; 182(4627): 64-5.
[2] Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4): 663-76.
[3] Crick F. Central dogma of molecular biology. Nature. 1970; 227(5258): 561-3.
[4] Waddington CH. The epigenotype. Endeavour. 1942;1:18–20.
[5] Goldschmidt R. Gen und Ausseneigenschaft. I Zeitschr ind Abstl 1935; 69 (38-69).
[6] Waddington CH, Pantelouris EM. Transplantation of nuclei in newt's eggs. Nature. 1953; 172(4388): 1050-1.
[7] Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986; 321(6067): 209-13.
[8] Wallrath LL, Elgin SC. Position effect variegation in Drosophila is associated with an altered chromatin structure. Genes Dev. 1995; 9(10): 1263-77.
[9] Grewal SI, Klar AJ. Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell. 1996; 86(1): 95-101.
[10] Mayr E. The Growth of Biological Thought: Diversity, Evolution, and Inheritance. Boston: Harvard University Press; 1982.
[11] Green CM, Almouzni G. When repair meets chromatin. First in series on chromatin dynamics. EMBO Rep. 2002; 3(1): 28-33.
[12] Ikura T, Ogryzko VV. Chromatin dynamics and DNA repair. Front Biosci. 2003; 8: s149-55.
[13] Viens A, Mechold U, Brouillard F, Gilbert C, Leclerc P, Ogryzko V. Analysis of human histone H2AZ deposition in vivo argues against its direct role in epigenetic templating mechanisms. Mol Cell Biol. 2006; 26(14): 5325-35.
[14] Ogryzko VV. Erwin Schroedinger, Francis Crick and epigenetic stability. Biol Direct. 2008; 3: 15.
[15] Lederberg J. The meaning of epigenetics The Scientist. 2001:15(18):6.
[16] Beisson J, Sonneborn TM. Cytoplasmic inheritance of the organization of the cell cortex in Paramecium aurelia. Proc Natl Acad Sci USA. 1965; 53: 275-82.
[17] Kleine Borgmann LA, Hummel H, Ulbrich MH, Graumann PL. SMC condensation centers in Bacillus subtilis are dynamic structures. J Bacteriol. 2013; 195(10): 2136-45.
[18] Kauffman SA. Metabolic stability and epigenesis in randomly constructed genetic nets. J Theor Biol. 1969; 22(3): 437-67.
[19] Fisher RA. The possible modification of the response of the wild type to recurrent mutations. Am Nat. 1928; 62(679): 115-26.
[20] Ptashne M. A Genetic Switch: Phage Lambda Revisited (3rd ed.). Cold Spring Harbor: Cold Harbor Spring Laboratory Press; 2004.
[21] Zhu XM, Yin L, Hood L, Ao P. Calculating biological behaviors of epigenetic states in the phage lambda life cycle. Funct Integr Genomics. 2004; 4(3): 188-95.
[22] Ptashne M. Binding reactions: epigenetic switches, signal transduction and cancer. Curr Biol. 2009; 19(6): R234-41.
[23] Halfmann R, Jarosz DF, Jones SK, Chang A, Lancaster AK, Lindquist S. Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature. 2012; 482(7385): 363-8.
[24] Holmes DL, Lancaster AK, Lindquist S, Halfmann R. Heritable remodeling of yeast multicellularity by an environmentally responsive prion. Cell. 2013; 153(1): 153-65.
[25] Crick F. Memory and molecular turnover. Nature. 1984; 312(5990): 101.
[26] Owen DJ, Ornaghi P, Yang JC, Lowe N, Evans PR, Ballario P, Neuhaus D, Filetici P, Travers AA. The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase gcn5p. EMBO J. 2000; 19(22): 6141-9.
[27] Jenuwein T, Allis CD. Translating the histone code. Science. 2001; 293(5532): 1074-80.
[28] Ogryzko VV. Mammalian histone acetyltransferases and their complexes. Cell Mol Life Sci. 2001; 58(5-6): 683-92.
[29] Hopfield JJ. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci USA. 1974; 71(10): 4135-9.
[30] Bender J. RNA-directed DNA methylation: getting a grip on mechanism. Curr Biol. 2012; 22(10): R400-1.
[31] Wassenegger M, Heimes S, Riedel L, Sanger HL. RNA-directed de novo methylation of genomic sequences in plants. Cell. 1994; 76(3): 567-76.
[32] Martienssen RA. Maintenance of heterochromatin by RNA interference of tandem repeats. Nat Genet. 2003; 35(3): 213-4.
[33] Wang F, Koyama N, Nishida H, Haraguchi T, Reith W, Tsukamoto T. The assembly and maintenance of heterochromatin initiated by transgene repeats are independent of the RNA interference pathway in mammalian cells. Mol Cell Biol. 2006; 26(11): 4028-40.