Cis-Acting 

This term is used in the context of regulation of gene transcription to denote DNA sequences that have to be physically joined to the genes in question to influence their activity. Trans-acting sequences, on the other hand, exert their regulatory effects regardless of whether or not they are present on the same chromosome as the regulated gene. Trans-acting genes generally encode proteins that bind to cis-acting DNA sequences.

Cis-acting sequences were classically identified as a result of their mutation, either silencing or activating the controlled gene, depending on whether the cis-acting sequence provided a binding site for RNA polymerase or other necessary transcriptional factor or for a repressor protein. These two kinds of cis-acting sequences, respectively positive and negative in their effect, were first identified in the Escherichia coli Lac operon, where they were called the promoter and operator sequences. With the development of recombinant DNA technology, it became possible to detect protein-binding sites in DNA without mutation (e.g., by footprinting or gel retardation assays), and then to determine their effects on transcription by “engineered” deletions.

Cis-acting sequences that act otherwise than by providing binding sites for regulatory proteins are comparatively uncommon, but two quite different examples should be mentioned. In bacterial operons, a mutation that causes premature translational termination of an upstream gene can cause a drastic reduction in the expression of genes in the same operon further downstream. This is a strictly cis-acting effect, acting within a single unit of transcription. The mechanism is explained under Lac Operon.

 The second example is from female mammals where one of the two X-chromosomes in each cell lineage is largely inactivated with the notable exception of one gene, active only in the otherwise “silent” X, that is transcribed into a long RNA molecule called Xist. This transcript, which does not encode a protein, plays an essential role in silencing the rest of the chromosome. It acts only in cis and remains associated with the chromosome from which it is transcribed without effect on the other, active, X-chromosome.

X-chromosome inactivation involves propagating a certain type of condensed and transcriptionally inactivating chromatin structure, generally called heterochromatin, which, in most chromosomes, is restricted to certain segments. In Drosophila melanogaster, heterochromatin exerts a cis-effect in suppressing gene activity when, as a result of segmental chromosomal rearrangement, it is brought close to genes not normally associated with it. The multiprotein heterochromatin complex spreads along the chromosome, inactivating the genes in its path with a probability that decreases with distance. Genes that are normally close to heterochromatin are apparently insulated in some way against this effect.