Transcriptional enhancers--on/off gene regulation as an adaptation to silencing in higher eukaryotic nuclei

Transcriptional enhancers are DNA elements that act at a distance from a gene to regulate its expression. Principally, they seem to antagonize gene silencing, but they can also influence transcription rate. The relative importance and functional relationship of these two processes remains unclear. Cell differentiation requires a stable program of gene expression, with some genes active and others silent. Enhancers could function in this process by preventing incorporation of genes into heterochromatin, thus allowing the expression of genes characteristic of the cell lineage. This hypothesis takes into account the ability of enhancers to antagonize silencing, the association of silenced genes with heterochromatin in differentiated cells, and disruption of that association by enhancers. Comparison with yeast suggests that in higher eukaryotes, stronger and more numerous activating elements have been made necessary by the formation of a powerfully repressive nuclear compartment during cell differentiation.