The regulation of gene expression in eukaryotes is achieved through the interaction of several levels of control that acts both locally to turn on or off individual genes in response to a specific cellular need and globally to maintain a chromatin-wide gene expression pattern that shapes cell identity. Because eukaryotic genome is wrapped around histones to form nucleosomes and higher-order chromatin structures, the substrates for transcriptional machinery are in general partially concealed. Without regulatory proteins, many genes are expressed at low level or not expressed at all. Transcription requires displacement of the positioned nucleosomes to enable the transcriptional machinery to gain access of the DNA.
All steps in the transcription are subject to some degree of regulation. Transcription initiation in particular is the primary level at which gene expression is regulated. Targeting the rate-limiting initial step is the most efficient in terms of energy costs for the cell. Transcription initiation is regulated by cis-acting elements (enhancers, silencers, isolators) within the regulatory regions of the DNA, and sequence-specific trans-acting factors that act as activators or repressors. Gene transcription can also be regulated post-initiation by targeting the movement of the elongating polymerase.