Epigenetic involvement

Figure 17.4. Epigenetics in the nervous system. Regulation occurs in response to synaptic inputs and/or other psychosocial-environmental stimuli. The external stimuli result in changes in the transcriptional profile of the neuron and eventually affects neural function(s). Many disorders of human cognition might involve dysfunction of epigenetic tagging. (See color insert.)...

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. 

The epigenetic codes set by HATs are countered by the activity of the histone deacetylases. This delicate balance has been documented to maintain the cellular homeostasis. HDACs seem to play dual opposing roles in disease manifestation. Dysfunctioning of HDACs are involved in several cancers. In some cases HDACs... 

Apart from this HDACs are also associated with a number of other epigenetic repression mechanisms including histone methylation, polycomb group of proteins and DNA methylation (discussed later). The class II HDACs have been found to be involved in muscle development, particularly HDAC 5 and 9 knockouts or mutants show evidence of cardiac hypertrophy in a age or stress dependent manner (Zhang et al, 2002 Chang et al, 2004). 

Several authors have successfully demonstrated the feasibility of targeting AD genes (e.g., APP-London mutation, APP-Swedish mutation, PSl, APLPl, APLP2, PEN-2, APH-la, Nicastrin, BACE, MAPP-V337M) with RNAi (418-423). Some authors have speculated about the possibility that ABP overproduction might be caused by the loss of epigenetic control in the expression of the genes involved in... 

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. 

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