Fig. 2.

The effect of different external signals depends on epigenetic modification in the target cells. The cellular response to external signals may reflect chromatin-based (epigenetic) differences superimposed on the static genetic code. In this example, the 5-regulatory region of a disease susceptibility gene is depicted in cells. In some cells, the promoter assumes an “open” chromatin architecture characterized by activated histone posttranslational marks, decreased nucleosome density, and the lack of DNA methylation. RNA polymerase II is recruited to the promoter, resulting in productive transcription. Alternatively, in other cells the genetically identical promoter assumes a “closed” chromatin configuration characterized by repressive posttranslational marks, increased nucleosome density, and prominent DNA methylation. RNA polymerase II is not recruited to the promoter, and no transcription occurs. Transcriptionally competent euchromatin is usually associated with unmethylated DNA, and trimethyl H3K4me3 and H3K36me3 marks. Transcription-ally incompetent heterochromatin is generally associated with methylated DNA and trimethyl H3K27 marks