Editorial [Hot Topic: Mini Hot Topic Title: Epigenetic Regulatory Mechanisms in Cancer, Development, and Evolution (Guest Editor: Douglas M. Ruden)]

Publisher： Bentham Science Publishers

E-ISSN： 1875-5488|6|3|127-127

ISSN： 1389-2029

Source： Current Genomics, Vol.6, Iss.3, 2005-05, pp. : 127-127

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Abstract

Conrad H. Waddington (1905-1975) is the developmental biologist generally known as the inventor of the term “epigenetics,” which literally means “outside of genetics” [1]. In modern usage, “epigenetics” refers to “all meiotically and mitotically heritable changes in gene expression that are not coded in the DNA sequence itself” [2]. Methylation of the C5 position of cytosine in DNA, 5meC, has been recognized as a principle epigenetic silencing mechanism since the 1970s [3]. The methylation of CpG sites within the genome in mammals is maintained by three classes of DNA methyltransferases (DNMTs) and has numerous roles from the silencing of transposable elements to the transcriptional repression of certain developmental genes [2].In the early 1980s, Feinberg and Vogelstein pioneered the field of cancer epigenetics by showing that tumor cells have generally hypomethylated DNA [4, 5]. Feinberg's laboratory subsequently showed that loss of DNA methylation is a general characteristic of tumor cells, but, paradoxically, hypermethylation at specific genes also occurs (reviewed in [6]). In the 20 years since these early studies, epigenetic regulation of gene expression in cancer and development has continued to increase in importance.This special issue features three papers that review emerging issues in epigenetic regulation. The first review, “The epigenetics of breast cancer carcinogenesis and metastasis,” by Phipps et al. discusses recent pharmacological interventions to inhibit the DNA methylation status in breast cancer cells. The role of DNA methylation in the maintenance of breast cancer stem cells and the implications for treating breast cancer is also discussed.The second review, “The epigenomic viewpoint on cellular differentiation of myeloid progenitor cells as it pertains to leukemogenesis,” by Sollars explores how epigenetic regulation controls the differentiation of myeloid lineages. Issues such as cellular memory and how it is influenced by the environment and the implications for treating leukemia will be discussed.Finally, in the third review, “Epigenetic regulation of trinucleotide repeat expansions and contractions and the ”biased embryos“ hypothesis for rapid morphological evolution,” members of my laboratory and I discuss recent evidence by Fondon and Garner that morphological evolution in dogs involves trinucleotide repeat expansions and contractions [7]. We noticed that vertebrate trinucleotide repeats often contain CpG dinucleotides, so we proposed a hypothesis that CpGs are hypomethylated during stress, and that this facilitates expansions and contractions of key developmental genes in germ cells.Obviously, the field of epigenetics is expanding so rapidly that it is impossible to cover all of the exciting new developments in this area. “Epigenomics,” which refers to global epigenetic regulatory mechanisms in cancer, development, evolution, and other areas, will continue being important topics for this journal.References[1] Van Speybroeck, L. From epigenesis to epigenetics: the case of C. H. Waddington. Annals of the New York Academy of Sciences 2002, 981: 61-81.[2] Egger, G., Liang, G., Aparicio, A., Jones, P.A. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004, 429(6990): 457-63.[3] Holliday, R., Pugh, J.E. DNA modification mechanisms and gene activity during development. Science 1975, 187(4173): 226-32.[4] Feinberg, A.P., Vogelstein, B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983, 301(5895): 89-92.[5] Feinberg, A.P., Vogelstein, B. Hypomethylation of ras oncogenes in primary human cancers. Biochemical & Biophysical Research Communications 1983, 111(1): 47-54.[6] Feinberg, A.P., Tycko, B. The history of cancer epigenetics. Nature Reviews Cancer 2004, 4(2): 143-53.[7] Fondon, J.W., Garner, H.R. Molecular origins of rapid and continuous morphological evolution. Proc. Natl. Acad. Sci. USA 2004, 101(52): 18058-63.

Abstract

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