Epigenetic mechanisms

In higher eukaiyotes, most of the chromosomal DNA carries 5-methyl-cytidine residues located in CpG sequence motives. There is a close correlation between transcriptional inactivation and methylation. On the other hand, considerable evidence shows that regions of DNA that are actively engaged in transcription lack 5-methyl-cytidine nucleotides in CpG motivs. Hence DNA methylation is a means how cells regulate gene expression. DNA methylation which is catalyzed by DNA methyltransferases is the best characterized epigenetic mechanism. 

To further investigate the role of genetic vs epigenetic mechanisms in the induction of the tumors, one can compare the response of rats to diesel soot to that elicited by the pure form of soot, carbon black. 

Carmichael PL, Mills JJ, Neven P (1998) An epigenetic mechanism for tamoxifen-associated uterine carcinogenesis Eur J Cancer 34(Suppl 4) S10-S11... 

Burchiel, S.W. et al., Analysis of genetic and epigenetic mechanisms of toxicity potential roles of toxicogenomics and proteomics in toxicology, Toxicol. Sci., 59, 193, 2001. 

Nonlinear response because of epigenetic mechanism (quadratic relation used as representative)... 

To Provide Mechanistic Insight. For example, if an agent is negative in a wide range of genetic toxicity screens, but still produces tumors in animals, then one could hypothesize that an epigenetic mechanism was involved. 

Williams GM. 1981. Liver carcinogenesis The role for some chemicals of an epigenetic mechanisms of liver-tumor promotion involving modification of the cell membrane. Food Cosmet Toxicol 19(5) 577- 583. 

Epigenetic is a term used to describe a state of gene expression that is mitotically and meiotically inherited without any change in the sequence of DNA. Epigenetic mechanisms are mainly of two classes (1) the DNA may be modified by the covalent attachment of a moiety that is then perpetuated. (2) a self-perpetuating protein state may be established (Zelent et al, 2004). The two most studied epigenetic phenomena are DNA methylation and histone tail modifications (Mai et ai, 2005). 

Russo, V., Martienssen, R., and Riggs, A. (1996) Epigenetic mechanisms of gene regulation. Cold Spring Harbor, NY Cold Spring Harbor Laboratory Press. 

Different mechanisms can lead to total or partial loss of HLA class 1 antigen expression. This could occur at any step of the MHC class 1 processing machinery and involves structural alterations, epigenetic mechanisms and dysregulation of various APM components. 

The notion that DNA methylation is an epigenetic mechanism that acts in conjunction with post-synthetic modifications of histones and other proteins is nowadays widely accepted and is the focus of major research effort worldwide. It must be noted though that this is probably not the only way through which methylation affects chromatin structure, and that DNA methylation may directly modulate some basic structural features of nucleosomes or the chromatin fibers they form. 

Hauser, A.-T. and Jung, M. (2008) Targeting Epigenetic Mechanisms Potential of Natural Products in Cancer Chemoprevention. Planta Medica (in press). 

Imprinting involves an epigenetic mechanism, ie, an alteration in phenotype that does not result from a change in the genotype. 

Angelman and Prader-Willi syndromes are related disorders affecting genes on chromosome 15 by which of the following epigenetic mechanisms ... 

Costa M. 1995. Model for the epigenetic mechanism of action of nongenotoxic carcinogens. Am J Clin Nutr 61(suppl) 666S-669S. 

GENERAL PRINCIPLES OF EPIGENETIC REGULATION 1.1. Epigenetic Mechanisms... 

Emerman M, Temin HM (1984), Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism, Cell 39 449-467. 

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