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By Moshe Szyf

NA methylation has bewildered molecular biologists when you consider that Hotchkiss chanced on it nearly six many years in the past (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). the truth that the chemical constitution of our D genome involves parts which are covalently sure, the genetic details that's replicated through the DNA replication equipment ana DNA methylation that's maintainea via self sustaining enzymatic equipment, has redictably prompted the mind's eye and interest of generations of mo­ Edular biologists. An seen query used to be even if DNA methylation was once a bearer of extra info to the genetic info and what used to be the character of this data? It used to be tempting to invest that DNA me­ thylation utilized a few kind of keep watch over over programming of the genome s expression profile. as soon as concepts to probe the methylation profile of complete genomes in addition to particular genes grew to become to be had, it turned transparent that DNA methylation styles are gene and tissue particular and that styles of gene expression correlate with styles of methylation. DNA methylation pat­ terns emerged because the basically component to the chemical constitution of DNA that exhibited tissue and mobilephone specificity. this knowledge probably supplied an attrac­ tively easy reason for the longstanding problem of the way may possibly one exact genome present itself in such a lot of assorted types in multicellular organisms? The DNA methylation trend has therefore develop into the one recognized issue to confer upon DNA a different mobile identification.

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Bird A. D N A methylation patterns and epigenetic memory. Genes Dev 2002; 16:6-21. 13. Yoder JA, Walsh CP, Bestor T H . Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 1997; 13:335-340. 14. Reik W, Dean W , Walter J. Epigenetic reprogramming in mammalian development. Science 2 0 0 1 ; 293:1089-1093. 15. Bird A. CpG-rich islands and the ftmction of D N A methylation. Nature 1986; 321:209-213. 16. Okano M , Xie S, Li E. D n m t 2 is not required for de novo and maintenance methylation of viral D N A in embryonic stem cells.

In another study by the same group, 53% of 32 examined prostate adenocarcinomas were found to have LINE-1 hypomethylation. "^^ Therefore, LINE-1 hypomethylation appears to vary in frequency between different types of cancers. Tandem DNA repeats are also frequently hypomethylated in human cancers, including satellite DNA sequences, which are found in constitutive heterochromatin. Hypomethylation of centromeric satellite OL DNA (Sata) and juxtacentromeric (centromere-adjacent) satellite 2 (Sat2) in chromosomes 1 and 16 was demonstrated in various cancers.

Bestor T , Laudano A, Mattaliano R et al. Cloning and sequencing of a c D N A encoding D N A methyltransferase of mouse cells. J Mol Biol 1988; 203:971-983. 7. Bestor T H . T h e D N A methyltransferases. H u m Mol Genet 2000; 9(16):2395-2402. 8. S m i t h SS, Kaplan BE, Sowers L C et al. M e c h a n i s m of h u m a n m e t h y l - d i r e c t e d D N A methyltransferase and the fidelity of cytosine methylation. Proc N a t l Acad Sci USA 1992; 89:4744-4748. 9. Baylin SB, Esteller M, Rountree M R et al.

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