Eukaryotic genes are often regulated by combinations of DNA sequences and proteins that control how efficiently transcription begins.

A transcription factor is a protein that binds DNA directly or interacts with other transcriptional proteins to influence transcription.

Promoters and general transcription machinery

Most eukaryotic protein-coding genes are transcribed by RNA polymerase II, one of the specialized eukaryotic RNA polymerases. A gene transcribed by RNA polymerase II has a core promoter near its transcription start site. General transcription factors assemble with the polymerase at this region to form a transcription-initiation complex.

This basal machinery is necessary for transcription but does not by itself explain why one gene is highly transcribed in one cell and nearly silent in another.

Enhancers, silencers and specific transcription factors

Additional cis-regulatory elements are DNA sequences that regulate genes located on the same DNA molecule.

• Enhancers contain binding sites whose bound regulators can increase transcription.
• Silencers contain sites whose bound regulators can reduce transcription.

These elements can lie far from the promoter in linear DNA sequence. Chromatin can loop so that proteins bound at distant regulatory elements interact with promoter-associated machinery.

Proteins that increase transcription are often called activators; proteins that reduce it are often called repressors.

Combinatorial control

A regulatory region commonly contains binding sites for several transcription factors. The transcriptional output depends on the combination of factors present and active in that cell.

For example, imagine that strong transcription requires activators A and B while repressor R blocks the promoter-associated complex. The same DNA sequence could then be highly transcribed in a cell containing A and B but little R, and weakly transcribed in another cell lacking B or containing active R.

This allows cells with essentially the same genome to transcribe different sets of genes.

Eukaryotic transcriptional regulation therefore does not behave like a single universal on/off switch. It is a sequence-specific, combinatorial process in which promoters and more distant regulatory elements integrate the activities of many DNA-binding proteins.