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The structure and function of eukaryotic enhancer elements and their role in oncogenesis.

Transcriptional enhancers have now been identified near or within a large number of viral and cellular genes. They are cis-acting regulatory sequences generally capable of elevating transcription from a linked gene in a distance and orientation independent manner. More recent evidence suggests that this activity may be modulated in a host-cell-specific manner. Enhancer function in some cases at least appears to be controlled by the operation of trans-acting factors within the host cell. Occasionally enhancers may also be responsible for repression of gene transcription. It has now become clear that the development of some cancers may be linked with the activity of enhancer sequences. It is likely that this process involves subversion of the normal regulatory mechanisms which control expression of proto-oncogenes through the interposition of exogenous, cis-acting enhancer sequences. The evidence comes from two sources, firstly a strong association between the action of enhancer sequences and some forms of naturally occurring cancers, and secondly, the induction of neoplastic transformation in susceptible cells by genetically manipulated oncogenes under the transcriptional control of enhancer elements.